Skip to main content

Advertisement

SpringerLink
Log in

CAS proteins in normal and pathological cell growth control

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Proteins of the CAS (Crk-associated substrate) family (BCAR1/p130Cas, NEDD9/HEF1/Cas-L, EFS/SIN and CASS4/HEPL) are integral players in normal and pathological cell biology. CAS proteins act as scaffolds to regulate protein complexes controlling migration and chemotaxis, apoptosis, cell cycle, and differentiation, and have more recently been linked to a role in progenitor cell function. Reflecting these complex functions, over-expression of CAS proteins has now been strongly linked to poor prognosis and increased metastasis in cancer, as well as resistance to first-line chemotherapeutics in multiple tumor types including breast and lung cancers, glioblastoma, and melanoma. Further, CAS proteins have also been linked to additional pathological conditions including inflammatory disorders, Alzheimer’s and Parkinson’s disease, as well as developmental defects. This review will explore the roles of the CAS proteins in normal and pathological states in the context of the many mechanistic insights into CAS protein function that have emerged in the past decade.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kanner SB, Reynolds AB, Parsons JT (1991) Tyrosine phosphorylation of a 120-kilodalton pp60src substrate upon epidermal growth factor and platelet-derived growth factor receptor stimulation and in polyomavirus middle-T-antigen-transformed cells. Mol Cell Biol 11:713–720

    CAS  PubMed  Google Scholar 

  2. Reynolds AB, Roesel DJ, Kanner SB, Parsons JT (1989) Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene. Mol Cell Biol 9:629–638

    CAS  PubMed  Google Scholar 

  3. Sakai R, Iwamatsu A, Hirano N, Ogawa S, Tanaka T, Mano H, Yazaki Y, Hirai H (1994) A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner. EMBO J 13:3748–3756

    CAS  PubMed  Google Scholar 

  4. Brinkman A, van der Flier S, Kok EM, Dorssers LC (2000) BCAR1, a human homologue of the adapter protein p130Cas, and antiestrogen resistance in breast cancer cells. J Natl Cancer Inst 92:112–120

    CAS  PubMed  Google Scholar 

  5. Ishino M, Ohba T, Sasaki H, Sasaki T (1995) Molecular cloning of a cDNA encoding a phosphoprotein, Efs, which contains a Src homology 3 domain and associates with Fyn. Oncogene 11:2331–2338

    CAS  PubMed  Google Scholar 

  6. Alexandropoulos K, Baltimore D (1996) Coordinate activation of c-Src by SH3- and SH2-binding sites on a novel p130Cas-related protein, Sin. Genes Dev 10:1341–1355

    CAS  PubMed  Google Scholar 

  7. Law SF, Estojak J, Wang B, Mysliwiec T, Kruh G, Golemis EA (1996) Human enhancer of filamentation 1, a novel p130cas-like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces cerevisiae. Mol Cell Biol 16:3327–3337

    CAS  PubMed  Google Scholar 

  8. Minegishi M, Tachibana K, Sato T, Iwata S, Nojima Y, Morimoto C (1996) Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes. J Exp Med 184:1365–1375

    CAS  PubMed  Google Scholar 

  9. Kumar S, Tomooka Y, Noda M (1992) Identification of a set of genes with developmentally down-regulated expression in the mouse brain. Biochem Biophys Res Commun 185:1155–1161

    CAS  PubMed  Google Scholar 

  10. Singh MK, Dadke D, Nicolas E, Serebriiskii IG, Apostolou S, Canutescu A, Egleston BL, Golemis EA (2008) A novel Cas family member, HEPL, regulates FAK and cell spreading. Mol Biol Cell 19:1627–1636

    CAS  PubMed  Google Scholar 

  11. Astier A, Manie SN, Avraham H, Hirai H, Law SF, Zhang Y, Golemis EA, Fu Y, Druker BJ, Haghayeghi N, Freedman AS, Avraham S (1997) The related adhesion focal tyrosine kinase differentially phosphorylates p130Cas and the Cas-like protein, p105HEF1. J Biol Chem 272:19719–19724

    CAS  PubMed  Google Scholar 

  12. Manie SN, Beck AR, Astier A, Law SF, Canty T, Hirai H, Druker BJ, Avraham H, Haghayeghi N, Sattler M, Salgia R, Griffin JD, Golemis EA, Freedman AS (1997) Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells. J Biol Chem 272:4230–4236

    CAS  PubMed  Google Scholar 

  13. Iwata S, Souta-Kuribara A, Yamakawa A, Sasaki T, Shimizu T, Hosono O, Kawasaki H, Tanaka H, Dang NH, Watanabe T, Arima N, Morimoto C (2005) HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L). Oncogene 24:1262–1271

    CAS  PubMed  Google Scholar 

  14. Hunter AJ, Shimizu Y (1997) Alpha 4 beta 1 integrin-mediated tyrosine phosphorylation in human T cells: characterization of Crk- and Fyn-associated substrates (pp105, pp115, and human enhancer of filamentation-1) and integrin-dependent activation of p59fyn1. J Immunol 159:4806–4814

    CAS  PubMed  Google Scholar 

  15. Kamiguchi K, Tachibana K, Iwata S, Ohashi Y, Morimoto C (1999) Cas-L is required for beta 1 integrin-mediated costimulation in human Tcells. J Immunol 163:563–568

    CAS  PubMed  Google Scholar 

  16. Ohashi Y, Iwata S, Kamiguchi K, Morimoto C (1999) Tyrosine phosphorylation of Crk-associated substrate lymphocyte-type Is a critical element in TCR- and {beta}1 integrin-induced T lymphocyte migration. J Immunol 163:3727–3734

    CAS  PubMed  Google Scholar 

  17. van Seventer GA, Salmen HJ, Law SF, O’Neill GM, Mullen MM, Franz AM, Kanner SB, Golemis EA, van Seventer JM (2001) Focal adhesion kinase regulates beta1 integrin-dependent T cell migration through an HEF1 effector pathway. Eur J Immunol 31:1417–1427

    PubMed  Google Scholar 

  18. Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF, Golemis EA, Griffin JD (1997) Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1). J Biol Chem 272:14320–14326

    CAS  PubMed  Google Scholar 

  19. Kirsch KH, Georgescu MM, Hanafusa H (1998) Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G. J Biol Chem 273:25673–25679

    CAS  PubMed  Google Scholar 

  20. Garton AJ, Burnham MR, Bouton AH, Tonks NK (1997) Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of protein tyrosine phosphatase substrate recognition. Oncogene 15:877–885

    CAS  PubMed  Google Scholar 

  21. Liu F, Sells MA, Chernoff J (1998) Protein tyrosine phosphatase 1B negatively regulates integrin signaling. Curr Biol 8:173–176

    CAS  PubMed  Google Scholar 

  22. Nakamoto T, Yamagata T, Sakai R, Ogawa S, Honda H, Ueno H, Hirano N, Yazaki Y, Hirai H (2000) CIZ, a zinc finger protein that interacts with p130(cas) and activates the expression of matrix metalloproteinases. Mol Cell Biol 20:1649–1658

    CAS  PubMed  Google Scholar 

  23. Harte MT, Hildebrand JD, Burnham MR, Bouton AH, Parsons JT (1996) p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase. J Biol Chem 271:13649–13655

    CAS  PubMed  Google Scholar 

  24. Wisniewska M, Bossenmaier B, Georges G, Hesse F, Dangl M, Kunkele KP, Ioannidis I, Huber R, Engh RA (2005) The 1.1 A resolution crystal structure of the p130cas SH3 domain and ramifications for ligand selectivity. J Mol Biol 347:1005–1014

    CAS  PubMed  Google Scholar 

  25. Petruzzelli L, Takami M, Herrera R (1996) Adhesion through the interaction of lymphocyte function-associated antigen-1 with intracellular adhesion molecule-1 induces tyrosine phosphorylation of p130cas and its association with c-CrkII. J Biol Chem 271:7796–7801

    CAS  PubMed  Google Scholar 

  26. Nojima Y, Morino N, Mimura T, Hamasaki K, Furuya H, Sakai R, Sato T, Tachibana K, Morimoto C, Yazaki Y et al (1995) Integrin-mediated cell adhesion promotes tyrosine phosphorylation of p130Cas, a Src homology 3-containing molecule having multiple Src homology 2-binding motifs. J Biol Chem 270:15398–15402

    CAS  PubMed  Google Scholar 

  27. Salgia R, Pisick E, Sattler M, Li JL, Uemura N, Wong WK, Burky SA, Hirai H, Chen LB, Griffin JD (1996) p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene. J Biol Chem 271:25198–25203

    CAS  PubMed  Google Scholar 

  28. Ishino M, Ohba T, Inazawa J, Sasaki H, Ariyama Y, Sasaki T (1997) Identification of an Efs isoform that lacks the SH3 domain and chromosomal mapping of human Efs. Oncogene 15:1741–1745

    CAS  PubMed  Google Scholar 

  29. Kostic A, Sheetz MP (2006) Fibronectin rigidity response through Fyn and p130Cas recruitment to the leading edge. Mol Biol Cell 17:2684–2695

    CAS  PubMed  Google Scholar 

  30. Sawada Y, Tamada M, Dubin-Thaler BJ, Cherniavskaya O, Sakai R, Tanaka S, Sheetz MP (2006) Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell 127:1015–1026

    CAS  PubMed  Google Scholar 

  31. Garron ML, Arsenieva D, Zhong J, Bloom AB, Lerner A, O’Neill GM, Arold ST (2009) Structural insights into the association between BCAR3 and Cas family members, an atypical complex implicated in anti-oestrogen resistance. J Mol Biol 386:190–203

    CAS  PubMed  Google Scholar 

  32. Briknarova K, Nasertorabi F, Havert ML, Eggleston E, Hoyt DW, Li C, Olson AJ, Vuori K, Ely KR (2005) The serine-rich domain from Crk-associated substrate (p130cas) is a four-helix bundle. J Biol Chem 280:21908–21914

    CAS  PubMed  Google Scholar 

  33. Vuori K, Hirai H, Aizawa S, Ruoslahti E (1996) Introduction of p130cas signaling complex formation upon integrin-mediated cell adhesion: a role for Src family kinases. Mol Cell Biol 16:2606–2613

    CAS  PubMed  Google Scholar 

  34. O’Neill GM, Golemis EA (2001) Proteolysis of the docking protein HEF1 and implications for focal adhesion dynamics. Mol Cell Biol 21:5094–5108

    PubMed  Google Scholar 

  35. Law SF, Zhang YZ, Fashena SJ, Toby G, Estojak J, Golemis EA (1999) Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain. Exp Cell Res 252:224–235

    CAS  PubMed  Google Scholar 

  36. Nakamoto T, Sakai R, Ozawa K, Yazaki Y, Hirai H (1996) Direct binding of C-terminal region of p130Cas to SH2 and SH3 domains of Src kinase. J Biol Chem 271:8959–8965

    CAS  PubMed  Google Scholar 

  37. Nasertorabi F, Tars K, Becherer K, Kodandapani R, Liljas L, Vuori K, Ely KR (2006) Molecular basis for regulation of Src by the docking protein p130Cas. J Mol Recognit 19:30–38

    CAS  PubMed  Google Scholar 

  38. Sakakibara A, Ohba Y, Kurokawa K, Matsuda M, Hattori S (2002) Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-pathway-mediated Rap1 activation. J Cell Sci 115:4915–4924

    CAS  PubMed  Google Scholar 

  39. Cai D, Felekkis KN, Near RI, O’Neill GM, van Seventer JM, Golemis EA, Lerner A (2003) The GDP exchange factor AND-34 is expressed in B cells, associates with HEF1, and activates Cdc42. J Immunol 170:969–978

    CAS  PubMed  Google Scholar 

  40. Feng L, Guedes S, Wang T (2004) Atrophin-1-interacting protein 4/human Itch is a ubiquitin E3 ligase for human enhancer of filamentation 1 in transforming growth factor-beta signaling pathways. J Biol Chem 279:29681–29690

    CAS  PubMed  Google Scholar 

  41. Nourry C, Maksumova L, Pang M, Liu X, Wang T (2004) Direct interaction between Smad3, APC10, CDH1 and HEF1 in proteasomal degradation of HEF1. BMC Cell Biol 5:20

    PubMed  Google Scholar 

  42. Pellicena P, Miller WT (2001) Processive phosphorylation of p130Cas by Src depends on SH3-polyproline interactions. J Biol Chem 276:28190–28196

    CAS  PubMed  Google Scholar 

  43. Law SF, O’Neill GM, Fashena SJ, Einarson MB, Golemis EA (2000) The docking protein HEF1 is an apoptotic mediator at focal adhesion sites. Mol Cell Biol 20:5184–5195

    CAS  PubMed  Google Scholar 

  44. Law SF, Zhang YZ, Klein-Szanto AJ, Golemis EA (1998) Cell cycle-regulated processing of HEF1 to multiple protein forms differentially targeted to multiple subcellular compartments. Mol Cell Biol 18:3540–3551

    CAS  PubMed  Google Scholar 

  45. Kook S, Shim SR, Choi SJ, Ahnn J, Kim JI, Eom SH, Jung YK, Paik SG, Song WK (2000) Caspase-mediated cleavage of p130cas in etoposide-induced apoptotic Rat-1 cells. Mol Biol Cell 11:929–939

    CAS  PubMed  Google Scholar 

  46. Petch LA, Bockholt SM, Bouton A, Parsons JT, Burridge K (1995) Adhesion-induced tyrosine phosphorylation of the p130 src substrate. J Cell Sci 108:1371–1379

    CAS  PubMed  Google Scholar 

  47. Polte TR, Hanks SK (1995) Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas. Proc Natl Acad Sci USA 92:10678–10682

    CAS  PubMed  Google Scholar 

  48. Ohba T, Ishino M, Aoto H, Sasaki T (1998) Interaction of two proline-rich sequences of cell adhesion kinase beta with SH3 domains of p130Cas-related proteins and a GTPase-activating protein, Graf. Biochem J 330(Pt 3):1249–1254

    CAS  PubMed  Google Scholar 

  49. Nakamoto T, Sakai R, Honda H, Ogawa S, Ueno H, Suzuki T, Aizawa S, Yazaki Y, Hirai H (1997) Requirements for localization of p130cas to focal adhesions. Mol Cell Biol 17:3884–3897

    CAS  PubMed  Google Scholar 

  50. Polte TR, Hanks SK (1997) Complexes of focal adhesion kinase (FAK) and Crk-associated substrate [p130(Cas)] are elevated in cytoskeleton-associated fractions following adhesion and Src transformation. Requirements for Src kinase activity and FAK proline-rich motifs. J Biol Chem 272:5501–5509

    CAS  PubMed  Google Scholar 

  51. Makkinje A, Near RI, Infusini G, Vanden Borre P, Bloom A, Cai D, Costello CE, Lerner A (2009) AND-34/BCAR3 regulates adhesion-dependent p130Cas serine phosphorylation and breast cancer cell growth pattern. Cell Signal 21:1423–1435

    CAS  PubMed  Google Scholar 

  52. Pugacheva EN, Golemis EA (2005) The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome. Nat Cell Biol 7:937–946

    CAS  PubMed  Google Scholar 

  53. Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (2007) HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 129:1351–1363

    CAS  PubMed  Google Scholar 

  54. Donaldson JC, Dempsey PJ, Reddy S, Bouton AH, Coffey RJ, Hanks SK (2000) Crk-associated substrate p130Cas interacts with nephrocystin and both proteins localize to cell–cell contacts of polarized epithelial cells. Exp Cell Res 256:168–178

    CAS  PubMed  Google Scholar 

  55. Kim W, Kook S, Kim DJ, Teodorof C, Song WK (2004) The 31-kDa caspase-generated cleavage product of p130cas functions as a transcriptional repressor of E2A in apoptotic cells. J Biol Chem 279:8333–8342

    CAS  PubMed  Google Scholar 

  56. Defilippi P, Di Stefano P, Cabodi S (2006) p130Cas: a versatile scaffold in signaling networks. Trends Cell Biol 16:257–263

    CAS  PubMed  Google Scholar 

  57. Honda H, Oda H, Nakamoto T, Honda Z, Sakai R, Suzuki T, Saito T, Nakamura K, Nakao K, Ishikawa T, Katsuki M, Yazaki Y, Hirai H (1998) Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas. Nat Genet 19:361–365

    CAS  PubMed  Google Scholar 

  58. Astier A, Manie SN, Law SF, Canty T, Haghayghi N, Druker BJ, Salgia R, Golemis EA, Freedman AS (1997) Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: potential relevance to neoplastic lymphohematopoietic cells. Leuk Lymphoma 28:65–72

    CAS  PubMed  Google Scholar 

  59. Kanda H, Mimura T, Morino N, Hamasaki K, Nakamoto T, Hirai H, Morimoto C, Yazaki Y, Nojima Y (1997) Ligation of the T cell antigen receptor induces tyrosine phosphorylation of p105CasL, a member of the p130Cas-related docking protein family, and its subsequent binding to the Src homology 2 domain of c-Crk. Eur J Immunol 27:2113–2117

    CAS  PubMed  Google Scholar 

  60. Natarajan M, Stewart JE, Golemis EA, Pugacheva EN, Alexandropoulos K, Cox BD, Wang W, Grammer JR, Gladson CL (2006) HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells. Oncogene 25:1721–1732

    CAS  PubMed  Google Scholar 

  61. Thao le B, Vu HA, Yasuda K, Taniguchi S, Yagasaki F, Taguchi T, Watanabe T, Sato Y (2009) Cas-L was overexpressed in imatinib-resistant gastrointestinal stromal tumor cells. Cancer Biol Ther 8:683–688

    Article  PubMed  Google Scholar 

  62. Kim M, Gans JD, Nogueira C, Wang A, Paik JH, Feng B, Brennan C, Hahn WC, Cordon-Cardo C, Wagner SN, Flotte TJ, Duncan LM, Granter SR, Chin L (2006) Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Cell 125:1269–1281

    CAS  PubMed  Google Scholar 

  63. Merrill RA, See AW, Wertheim ML, Clagett-Dame M (2004) Crk-associated substrate (Cas) family member, NEDD9, is regulated in human neuroblastoma cells and in the embryonic hindbrain by all-trans retinoic acid. Dev Dyn 231:564–575

    CAS  PubMed  Google Scholar 

  64. Merrill RA, Ahrens JM, Kaiser ME, Federhart KS, Poon VY, Clagett-Dame M (2004) All-trans retinoic acid-responsive genes identified in the human SH-SY5Y neuroblastoma cell line and their regulated expression in the nervous system of early embryos. Biol Chem 385:605–614

    CAS  PubMed  Google Scholar 

  65. Liu X, Elia AE, Law SF, Golemis EA, Farley J, Wang T (2000) A novel ability of Smad3 to regulate proteasomal degradation of a Cas family member HEF1. EMBO J 19:6759–6769

    CAS  PubMed  Google Scholar 

  66. Zheng M, McKeown-Longo PJ (2002) Regulation of HEF1 expression and phosphorylation by TGF-beta 1 and cell adhesion. J Biol Chem 277:39599–39608

    CAS  PubMed  Google Scholar 

  67. Richer JK, Jacobsen BM, Manning NG, Abel MG, Wolf DM, Horwitz KB (2002) Differential gene regulation by the two progesterone receptor isoforms in human breast cancer cells. J Biol Chem 277:5209–5218

    CAS  PubMed  Google Scholar 

  68. Buterin T, Koch C, Naegeli H (2006) Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis 27:1567–1578

    CAS  PubMed  Google Scholar 

  69. Monroe DG, Getz BJ, Johnsen SA, Riggs BL, Khosla S, Spelsberg TC (2003) Estrogen receptor isoform-specific regulation of endogenous gene expression in human osteoblastic cell lines expressing either ERalpha or ERbeta. J Cell Biochem 90:315–326

    CAS  PubMed  Google Scholar 

  70. Martin-Rendon E, Hale SJ, Ryan D, Baban D, Forde SP, Roubelakis M, Sweeney D, Moukayed M, Harris AL, Davies K, Watt SM (2007) Transcriptional profiling of human cord blood CD133 + and cultured bone marrow mesenchymal stem cells in response to hypoxia. Stem Cells 25:1003–1012

    CAS  PubMed  Google Scholar 

  71. Aquino JB, Lallemend F, Marmigere F, Adameyko II, Golemis EA, Ernfors P (2009) The retinoic acid inducible Cas-family signaling protein Nedd9 regulates neural crest cell migration by modulating adhesion and actin dynamics. Neuroscience 162:1106–1119

    CAS  PubMed  Google Scholar 

  72. Vogel T, Ahrens S, Buttner N, Krieglstein K (2009) Transforming growth factor {beta} promotes neuronal cell fate of mouse cortical and hippocampal progenitors in vitro and in vivo: identification of Nedd9 as an essential signaling component. Cereb Cortex (in press)

  73. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–956

    CAS  PubMed  Google Scholar 

  74. Bui LC, Tomkiewicz C, Chevallier A, Pierre S, Bats AS, Mota S, Raingeaud J, Pierre J, Diry M, Transy C, Garlatti M, Barouki R, Coumoul X (2009) Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity. Oncogene (in press)

  75. Tran DH, Satou K, Ho TB (2008) Finding microRNA regulatory modules in human genome using rule induction. BMC Bioinformatics 9(Suppl 12):S5

    PubMed  Google Scholar 

  76. Schlaepfer DD, Broome MA, Hunter T (1997) Fibronectin-stimulated signaling from a focal adhesion kinase-c-Src complex: involvement of the Grb2, p130cas, and Nck adaptor proteins. Mol Cell Biol 17:1702–1713

    CAS  PubMed  Google Scholar 

  77. Tachibana K, Urano T, Fujita H, Ohashi Y, Kamiguchi K, Iwata S, Hirai H, Morimoto C (1997) Tyrosine phosphorylation of Crk-associated substrates by focal adhesion kinase. A putative mechanism for the integrin-mediated tyrosine phosphorylation of Crk-associated substrates. J Biol Chem 272:29083–29090

    CAS  PubMed  Google Scholar 

  78. Sanders MA, Basson MD (2005) p130Cas but not paxillin is essential for Caco-2 intestinal epithelial cell spreading and migration on collagen IV. J Biol Chem 280:23516–23522

    CAS  PubMed  Google Scholar 

  79. Schlaepfer DD, Hauck CR, Sieg DJ (1999) Signaling through focal adhesion kinase. Prog Biophys Mol Biol 71:435–478

    CAS  PubMed  Google Scholar 

  80. Cai D, Clayton LK, Smolyar A, Lerner A (1999) AND-34, a novel p130Cas-binding thymic stromal cell protein regulated by adhesion and inflammatory cytokines. J Immunol 163:2104–2112

    CAS  PubMed  Google Scholar 

  81. Cai D, Iyer A, Felekkis KN, Near RI, Luo Z, Chernoff J, Albanese C, Pestell RG, Lerner A (2003) AND-34/BCAR3, a GDP exchange factor whose overexpression confers antiestrogen resistance, activates Rac, PAK1, and the cyclin D1 promoter. Cancer Res 63:6802–6808

    CAS  PubMed  Google Scholar 

  82. Abassi YA, Rehn M, Ekman N, Alitalo K, Vuori K (2003) p130Cas Couples the tyrosine kinase Bmx/Etk with regulation of the actin cytoskeleton and cell migration. J Biol Chem 278:35636–35643

    CAS  PubMed  Google Scholar 

  83. Korah R, Choi L, Barrios J, Wieder R (2004) Expression of FGF-2 alters focal adhesion dynamics in migration-restricted MDA-MB-231 breast cancer cells. Breast Cancer Res Treat 88:17–28

    CAS  PubMed  Google Scholar 

  84. Avraham HK, Lee TH, Koh Y, Kim TA, Jiang S, Sussman M, Samarel AM, Avraham S (2003) Vascular endothelial growth factor regulates focal adhesion assembly in human brain microvascular endothelial cells through activation of the focal adhesion kinase and related adhesion focal tyrosine kinase. J Biol Chem 278:36661–36668

    CAS  PubMed  Google Scholar 

  85. Podar K, Shringarpure R, Tai YT, Simoncini M, Sattler M, Ishitsuka K, Richardson PG, Hideshima T, Chauhan D, Anderson KC (2004) Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib. Cancer Res 64:7500–7506

    CAS  PubMed  Google Scholar 

  86. Ceacareanu AC, Ceacareanu B, Zhuang D, Chang Y, Ray RM, Desai L, Chapman KE, Waters CM, Hassid A (2006) Nitric oxide attenuates IGF-I-induced aortic smooth muscle cell motility by decreasing Rac1 activity: essential role of PTP-PEST and p130cas. Am J Physiol Cell Physiol 290:C1263–C1270

    CAS  PubMed  Google Scholar 

  87. Nakamura I, Rodan GA, Duong le T (2003) Distinct roles of p130Cas and c-Cbl in adhesion-induced or macrophage colony-stimulating factor-mediated signaling pathways in prefusion osteoclasts. Endocrinology 144:4739–4741

    CAS  PubMed  Google Scholar 

  88. Rozengurt E (1998) Signal transduction pathways in the mitogenic response to G protein-coupled neuropeptide receptor agonists. J Cell Physiol 177:507–517

    CAS  PubMed  Google Scholar 

  89. Zhang Z, Baron R, Horne WC (2000) Integrin engagement, the actin cytoskeleton, and c-Src are required for the calcitonin-induced tyrosine phosphorylation of paxillin and HEF1, but not for calcitonin-induced Erk1/2 phosphorylation. J Biol Chem 275:37219–37223

    CAS  PubMed  Google Scholar 

  90. Zhang Z, Hernandez-Lagunas L, Horne WC, Baron R (1999) Cytoskeleton-dependent tyrosine phosphorylation of the p130(Cas) family member HEF1 downstream of the G protein-coupled calcitonin receptor. Calcitonin induces the association of HEF1, paxillin, and focal adhesion kinase. J Biol Chem 274:25093–25098

    CAS  PubMed  Google Scholar 

  91. Kovacic-Milivojevic B, Roediger F, Almeida EA, Damsky CH, Gardner DG, Ilic D (2001) Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte hypertrophy. Mol Biol Cell 12:2290–2307

    CAS  PubMed  Google Scholar 

  92. Jope RS, Song L, Grimes CA, Zhang L (1999) Oxidative stress oppositely modulates protein tyrosine phosphorylation stimulated by muscarinic G protein-coupled and epidermal growth factor receptors. J Neurosci Res 55:329–340

    CAS  PubMed  Google Scholar 

  93. Takahashi T, Kawahara Y, Taniguchi T, Yokoyama M (1998) Tyrosine phosphorylation and association of p130Cas and c-Crk II by ANG II in vascular smooth muscle cells. Am J Physiol 274:H1059–H1065

    CAS  PubMed  Google Scholar 

  94. Yang CC, Ogawa H, Dwinell MB, McCole DF, Eckmann L, Kagnoff MF (2005) Chemokine receptor CCR6 transduces signals that activate p130Cas and alter cAMP-stimulated ion transport in human intestinal epithelial cells. Am J Physiol Cell Physiol 288:C321–C328

    CAS  PubMed  Google Scholar 

  95. Cowell LN, Graham JD, Bouton AH, Clarke CL, O’Neill GM (2006) Tamoxifen treatment promotes phosphorylation of the adhesion molecules, p130Cas/BCAR1, FAK and Src, via an adhesion-dependent pathway. Oncogene 25:7597–7607

    CAS  PubMed  Google Scholar 

  96. Sasaki T, Iwata S, Okano HJ, Urasaki Y, Hamada J, Tanaka H, Dang NH, Okano H, Morimoto C (2005) Nedd9 protein, a Cas-L homologue, is upregulated after transient global ischemia in rats: possible involvement of Nedd9 in the differentiation of neurons after ischemia. Stroke 36:2457–2462

    CAS  PubMed  Google Scholar 

  97. Lee TN, Gold G, Workman R, Cook CA, Konrad RJ (2004) Glucose stimulates the association of Crk with p130Cas in pancreatic beta cells. Pancreas 29:e100–e105

    PubMed  Google Scholar 

  98. Ma A, Richardson A, Schaefer EM, Parsons JT (2001) Serine phosphorylation of focal adhesion kinase in interphase and mitosis: a possible role in modulating binding to p130Cas. Mol Biol Cell 12:1–12

    CAS  PubMed  Google Scholar 

  99. Yamakita Y, Totsukawa G, Yamashiro S, Fry D, Zhang X, Hanks SK, Matsumura F (1999) Dissociation of FAK/p130CAS/c-Src complex during mitosis: role of mitosis-specific serine phosphorylation of FAK. J Cell Biol 144:315–324

    CAS  PubMed  Google Scholar 

  100. Hoon Kim D, Jeon Choi S, Kook S, Kim W, Keun Song W (2003) Phosphorylation-dependent cleavage of p130cas in apoptotic rat-1 cells. Biochem Biophys Res Commun 300:141–148

    PubMed  Google Scholar 

  101. Wang X, Weng LP, Yu Q (2000) Specific inhibition of FGF-induced MAPK activation by the receptor-like protein tyrosine phosphatase LAR. Oncogene 19:2346–2353

    CAS  PubMed  Google Scholar 

  102. Weng LP, Wang X, Yu Q (1999) Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas. Genes Cells 4:185–196

    CAS  PubMed  Google Scholar 

  103. Garton AJ, Flint AJ, Tonks NK (1996) Identification of p130(cas) as a substrate for the cytosolic protein tyrosine phosphatase PTP-PEST. Mol Cell Biol 16:6408–6418

    CAS  PubMed  Google Scholar 

  104. Garton AJ, Tonks NK (1999) Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST. J Biol Chem 274:3811–3818

    CAS  PubMed  Google Scholar 

  105. Cote JF, Charest A, Wagner J, Tremblay ML (1998) Combination of gene targeting and substrate trapping to identify substrates of protein tyrosine phosphatases using PTP-PEST as a model. Biochemistry 37:13128–13137

    CAS  PubMed  Google Scholar 

  106. Sirois J, Cote JF, Charest A, Uetani N, Bourdeau A, Duncan SA, Daniels E, Tremblay ML (2006) Essential function of PTP-PEST during mouse embryonic vascularization, mesenchyme formation, neurogenesis and early liver development. Mech Dev 123:869–880

    CAS  PubMed  Google Scholar 

  107. Yo K, Iwata S, Hashizume Y, Kondo S, Nomura S, Hosono O, Kawasaki H, Tanaka H, Dang NH, Morimoto C (2009) SHP-2 inhibits tyrosine phosphorylation of Cas-L and regulates cell migration. Biochem Biophys Res Commun 382:210–214

    CAS  PubMed  Google Scholar 

  108. Noguchi T, Tsuda M, Takeda H, Takada T, Inagaki K, Yamao T, Fukunaga K, Matozaki T, Kasuga M (2001) Inhibition of cell growth and spreading by stomach cancer-associated protein-tyrosine phosphatase-1 (SAP-1) through dephosphorylation of p130cas. J Biol Chem 276:15216–15224

    CAS  PubMed  Google Scholar 

  109. Yokoyama N, Miller WT (2001) Protein phosphatase 2A interacts with the Src kinase substrate p130(CAS). Oncogene 20:6057–6065

    CAS  PubMed  Google Scholar 

  110. Zheng M, McKeown-Longo PJ (2006) Cell adhesion regulates Ser/Thr phosphorylation and proteasomal degradation of HEF1. J Cell Sci 119:96–103

    CAS  PubMed  Google Scholar 

  111. Hivert V, Pierre J, Raingeaud J (2009) Phosphorylation of human enhancer of filamentation (HEF1) on serine 369 induces its proteasomal degradation. Biochem Pharmacol 78:1017–1025

    CAS  PubMed  Google Scholar 

  112. Achiwa H, Lazo JS (2007) PRL-1 tyrosine phosphatase regulates c-Src levels, adherence, and invasion in human lung cancer cells. Cancer Res 67:643–650

    CAS  PubMed  Google Scholar 

  113. Daouti S, Li WH, Qian H, Huang KS, Holmgren J, Levin W, Reik L, McGady DL, Gillespie P, Perrotta A, Bian H, Reidhaar-Olson JF, Bliss SA, Olivier AR, Sergi JA, Fry D, Danho W, Ritland S, Fotouhi N, Heimbrook D, Niu H (2008) A selective phosphatase of regenerating liver phosphatase inhibitor suppresses tumor cell anchorage-independent growth by a novel mechanism involving p130Cas cleavage. Cancer Res 68:1162–1169

    CAS  PubMed  Google Scholar 

  114. Sorokin A, Reed E (1998) Insulin stimulates the tyrosine dephosphorylation of docking protein p130cas (Crk-associated substrate), promoting the switch of the adaptor protein crk from p130cas to newly phosphorylated insulin receptor substrate-1. Biochem J 334:595–600

    CAS  PubMed  Google Scholar 

  115. Black DS, Bliska JB (1997) Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions. EMBO J 16:2730–2744

    CAS  PubMed  Google Scholar 

  116. Persson C, Carballeira N, Wolf-Watz H, Fallman M (1997) The PTPase YopH inhibits uptake of Yersinia, tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions. EMBO J 16:2307–2318

    CAS  PubMed  Google Scholar 

  117. Bruce-Staskal PJ, Weidow CL, Gibson JJ, Bouton AH (2002) Cas, Fak and Pyk2 function in diverse signaling cascades to promote Yersinia uptake. J Cell Sci 115:2689–2700

    CAS  PubMed  Google Scholar 

  118. Bannerman DD, Sathyamoorthy M, Goldblum SE (1998) Bacterial lipopolysaccharide disrupts endothelial monolayer integrity and survival signaling events through caspase cleavage of adherens junction proteins. J Biol Chem 273:35371–35380

    CAS  PubMed  Google Scholar 

  119. Fashena SJ, Einarson MB, O’Neill GM, Patriotis C, Golemis EA (2002) Dissection of HEF1-dependent functions in motility and transcriptional regulation. J Cell Sci 115:99–111

    CAS  PubMed  Google Scholar 

  120. Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA (1998) CAS/Crk coupling serves as a “molecular switch” for induction of cell migration. J Cell Biol 140:961–972

    CAS  PubMed  Google Scholar 

  121. Vuori K, Ruoslahti E (1995) Tyrosine phosphorylation of p130Cas and cortactin accompanies integrin-mediated cell adhesion to extracellular matrix. J Biol Chem 270:22259–22262

    CAS  PubMed  Google Scholar 

  122. Cary LA, Han DC, Polte TR, Hanks SK, Guan JL (1998) Identification of p130Cas as a mediator of focal adhesion kinase-promoted cell migration. J Cell Biol 140:211–221

    CAS  PubMed  Google Scholar 

  123. Nakamura I, Jimi E, Duong LT, Sasaki T, Takahashi N, Rodan GA, Suda T (1998) Tyrosine phosphorylation of p130Cas is involved in actin organization in osteoclasts. J Biol Chem 273:11144–11149

    CAS  PubMed  Google Scholar 

  124. Moro L, Dolce L, Cabodi S, Bergatto E, Boeri Erba E, Smeriglio M, Turco E, Retta SF, Giuffrida MG, Venturino M, Godovac-Zimmermann J, Conti A, Schaefer E, Beguinot L, Tacchetti C, Gaggini P, Silengo L, Tarone G, Defilippi P (2002) Integrin-induced epidermal growth factor (EGF) receptor activation requires c-Src and p130Cas and leads to phosphorylation of specific EGF receptor tyrosines. J Biol Chem 277:9405–9414

    CAS  PubMed  Google Scholar 

  125. Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M (1998) Activation of Rac1 by a Crk SH3-binding protein, DOCK180. Genes Dev 12:3331–3336

    CAS  PubMed  Google Scholar 

  126. Feller SM, Posern G, Voss J, Kardinal C, Sakkab D, Zheng J, Knudsen BS (1998) Physiological signals and oncogenesis mediated through Crk family adapter proteins. J Cell Physiol 177:535–552

    CAS  PubMed  Google Scholar 

  127. Kanda H, Mimura T, Hamasaki K, Yamamoto K, Yazaki Y, Hirai H, Nojima Y (1999) Fyn and Lck tyrosine kinases regulate tyrosine phosphorylation of p105CasL, a member of the p130Cas docking protein family, in T-cell receptor-mediated signalling. Immunology 97:56–61

    CAS  PubMed  Google Scholar 

  128. O’Neill GM, Fashena SJ, Golemis EA (2000) Integrin signalling: a new Cas(t) of characters enters the stage. Trends Cell Biol 10:111–119

    PubMed  Google Scholar 

  129. Ridley AJ (2001) Rho GTPases and cell migration. J Cell Sci 114:2713–2722

    CAS  PubMed  Google Scholar 

  130. Simpson KJ, Selfors LM, Bui J, Reynolds A, Leake D, Khvorova A, Brugge JS (2008) Identification of genes that regulate epithelial cell migration using an siRNA screening approach. Nat Cell Biol 10:1027–1038

    CAS  PubMed  Google Scholar 

  131. Smith HW, Marra P, Marshall CJ (2008) uPAR promotes formation of the p130Cas-Crk complex to activate Rac through DOCK180. J Cell Biol 182:777–790

    CAS  PubMed  Google Scholar 

  132. Furuya K, Nakamoto T, Shen ZJ, Tsuji K, Nifuji A, Hirai H, Noda M (2000) Overexpression of Cas-interacting zinc finger protein (CIZ) suppresses proliferation and enhances expression of type I collagen gene in osteoblast-like MC3T3E1 cells. Exp Cell Res 261:329–335

    CAS  PubMed  Google Scholar 

  133. Janssen H, Marynen P (2006) Interaction partners for human ZNF384/CIZ/NMP4–zyxin as a mediator for p130CAS signaling? Exp Cell Res 312:1194–1204

    CAS  PubMed  Google Scholar 

  134. Pratt SJ, Epple H, Ward M, Feng Y, Braga VM, Longmore GD (2005) The LIM protein Ajuba influences p130Cas localization and Rac1 activity during cell migration. J Cell Biol 168:813–824

    CAS  PubMed  Google Scholar 

  135. Yi J, Kloeker S, Jensen CC, Bockholt S, Honda H, Hirai H, Beckerle MC (2002) Members of the Zyxin family of LIM proteins interact with members of the p130Cas family of signal transducers. J Biol Chem 277:9580–9589

    CAS  PubMed  Google Scholar 

  136. Dolfi F, Garcia-Guzman M, Ojaniemi M, Nakamura H, Matsuda M, Vuori K (1998) The adaptor protein Crk connects multiple cellular stimuli to the JNK signaling pathway. Proc Natl Acad Sci USA 95:15394–15399

    CAS  PubMed  Google Scholar 

  137. Fagerstrom S, Pahlman S, Nanberg E (1998) Protein kinase C-dependent tyrosine phosphorylation of p130cas in differentiating neuroblastoma cells. J Biol Chem 273:2336–2343

    CAS  PubMed  Google Scholar 

  138. Gustavsson A, Yuan M, Fallman M (2004) Temporal dissection of beta1-integrin signaling indicates a role for p130Cas-Crk in filopodia formation. J Biol Chem 279:22893–22901

    CAS  PubMed  Google Scholar 

  139. Alexander NR, Branch KM, Parekh A, Clark ES, Iwueke IC, Guelcher SA, Weaver AM (2008) Extracellular matrix rigidity promotes invadopodia activity. Curr Biol 18:1295–1299

    CAS  PubMed  Google Scholar 

  140. Cho SY, Klemke RL (2002) Purification of pseudopodia from polarized cells reveals redistribution and activation of Rac through assembly of a CAS/Crk scaffold. J Cell Biol 156:725–736

    CAS  PubMed  Google Scholar 

  141. Zaidel-Bar R, Kam Z, Geiger B (2005) Polarized downregulation of the paxillin-p130CAS-Rac1 pathway induced by shear flow. J Cell Sci 118:3997–4007

    CAS  PubMed  Google Scholar 

  142. Dadke D, Jarnik M, Pugacheva EN, Singh MK, Golemis EA (2006) Deregulation of HEF1 impairs M-phase progression by disrupting the RhoA activation cycle. Mol Biol Cell 17:1204–1217

    CAS  PubMed  Google Scholar 

  143. Bargon SD, Gunning PW, O’Neill GM (2005) The Cas family docking protein, HEF1, promotes the formation of neurite-like membrane extensions. Biochim Biophys Acta 1746:143–154

    CAS  PubMed  Google Scholar 

  144. Kyaw M, Yoshizumi M, Tsuchiya K, Kagami S, Izawa Y, Fujita Y, Ali N, Kanematsu Y, Toida K, Ishimura K, Tamaki T (2004) Src and Cas are essentially but differentially involved in angiotensin II-stimulated migration of vascular smooth muscle cells via extracellular signal-regulated kinase 1/2 and c-Jun NH2-terminal kinase activation. Mol Pharmacol 65:832–841

    CAS  PubMed  Google Scholar 

  145. Wendt MK, Smith JA, Schiemann WP (2009) p130Cas is required for mammary tumor growth and transforming growth factor-{beta} (TGF-{beta})-mediated metastasis through regulation of Smad2/3 activity. J Biol Chem (in press)

  146. Gingras D, Michaud M, Di Tomasso G, Beliveau E, Nyalendo C, Beliveau R (2008) Sphingosine-1-phosphate induces the association of membrane-type 1 matrix metalloproteinase with p130Cas in endothelial cells. FEBS Lett 582:399–404

    CAS  PubMed  Google Scholar 

  147. Imhof BA, Aurrand-Lions M (2004) Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol 4:432–444

    CAS  PubMed  Google Scholar 

  148. Regelmann AG, Danzl NM, Wanjalla C, Alexandropoulos K (2006) The hematopoietic isoform of Cas-Hef1-associated signal transducer regulates chemokine-induced inside-out signaling and T cell trafficking. Immunity 25:907–918

    CAS  PubMed  Google Scholar 

  149. Gotoh T, Cai D, Tian X, Feig LA, Lerner A (2000) p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine nucleotide exchange factor. J Biol Chem 275:30118–30123

    CAS  PubMed  Google Scholar 

  150. Hisakawa N, Tanaka H, Hosono O, Nishijima R, Ohashi Y, Saito S, Nishiya K, Hashimoto K, Morimoto C (2002) Aberrant responsiveness to RANTES in synovial fluid T cells from patients with rheumatoid arthritis. J Rheumatol 29:1124–1134

    CAS  PubMed  Google Scholar 

  151. Yu HG, Schrader H, Otte JM, Schmidt WE, Schmitz F (2004) Rapid tyrosine phosphorylation of focal adhesion kinase, paxillin, and p130Cas by gastrin in human colon cancer cells. Biochem Pharmacol 67:135–146

    CAS  PubMed  Google Scholar 

  152. Dutt P, Wang JF, Groopman JE (1998) Stromal cell-derived factor-1 alpha and stem cell factor/kit ligand share signaling pathways in hemopoietic progenitors: a potential mechanism for cooperative induction of chemotaxis. J Immunol 161:3652–3658

    CAS  PubMed  Google Scholar 

  153. Wang JF, Park IW, Groopman JE (2000) Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C. Blood 95:2505–2513

    CAS  PubMed  Google Scholar 

  154. Zhang XF, Wang JF, Matczak E, Proper JA, Groopman JE (2001) Janus kinase 2 is involved in stromal cell-derived factor-1alpha-induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells. Blood 97:3342–3348

    CAS  PubMed  Google Scholar 

  155. Fernandis AZ, Cherla RP, Ganju RK (2003) Differential regulation of CXCR4-mediated T-cell chemotaxis and mitogen-activated protein kinase activation by the membrane tyrosine phosphatase, CD45. J Biol Chem 278:9536–9543

    CAS  PubMed  Google Scholar 

  156. Seo S, Asai T, Saito T, Suzuki T, Morishita Y, Nakamoto T, Ichikawa M, Yamamoto G, Kawazu M, Yamagata T, Sakai R, Mitani K, Ogawa S, Kurokawa M, Chiba S, Hirai H (2005) Crk-associated substrate lymphocyte type is required for lymphocyte trafficking and marginal zone B cell maintenance. J Immunol 175:3492–3501

    CAS  PubMed  Google Scholar 

  157. Donlin LT, Danzl NM, Wanjalla C, Alexandropoulos K (2005) Deficiency in expression of the signaling protein sin/efs leads to t-lymphocyte activation and mucosal inflammation. Mol Cell Biol 25:11035–11046

    CAS  PubMed  Google Scholar 

  158. Rosenblatt J, Raff MC, Cramer LP (2001) An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism. Curr Biol 11:1847–1857

    CAS  PubMed  Google Scholar 

  159. Frisch SM, Francis H (1994) Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124:619–626

    CAS  PubMed  Google Scholar 

  160. Frisch SM, Screaton RA (2001) Anoikis mechanisms. Curr Opin Cell Biol 13:555–562

    CAS  PubMed  Google Scholar 

  161. Wei L, Yang Y, Zhang X, Yu Q (2004) Cleavage of p130Cas in anoikis. J Cell Biochem 91:325–335

    CAS  PubMed  Google Scholar 

  162. Bhattacharya S, Guo H, Ray RM, Johnson LR (2007) Basic helix-loop-helix protein E47-mediated p21Waf1/Cip1 gene expression regulates apoptosis of intestinal epithelial cells. Biochem J 407:243–254

    CAS  PubMed  Google Scholar 

  163. Wei L, Yang Y, Zhang X, Yu Q (2002) Anchorage-independent phosphorylation of p130(Cas) protects lung adenocarcinoma cells from anoikis. J Cell Biochem 87:439–449

    CAS  PubMed  Google Scholar 

  164. Wendt MK, Drury LJ, Vongsa RA, Dwinell MB (2008) Constitutive CXCL12 expression induces anoikis in colorectal carcinoma cells. Gastroenterology 135:508–517

    CAS  PubMed  Google Scholar 

  165. Cabodi S, Tinnirello A, Di Stefano P, Bisaro B, Ambrosino E, Castellano I, Sapino A, Arisio R, Cavallo F, Forni G, Glukhova M, Silengo L, Altruda F, Turco E, Tarone G, Defilippi P (2006) p130Cas as a new regulator of mammary epithelial cell proliferation, survival, and HER2-neu oncogene-dependent breast tumorigenesis. Cancer Res 66:4672–4680

    CAS  PubMed  Google Scholar 

  166. Brinkman A, de Jong D, Tuinman S, Azaouagh N, van Agthoven T, Dorssers LC (2009) The substrate domain of BCAR1 is essential for anti-estrogen-resistant proliferation of human breast cancer cells. Breast Cancer Res Treat (in press)

  167. van der Flier S, Brinkman A, Look MP, Kok EM, Meijer-van Gelder ME, Klijn JG, Dorssers LC, Foekens JA (2000) Bcar1/p130Cas protein and primary breast cancer: prognosis and response to tamoxifen treatment. J Natl Cancer Inst 92:120–127

    PubMed  Google Scholar 

  168. Casanova I, Bosch R, Lasa A, Parreno M, Cespedes MV, Brunet S, Nomdedeu JF, Mangues MA, Sierra J, Mangues R (2008) A celecoxib derivative inhibits focal adhesion signaling and induces caspase-8-dependent apoptosis in human acute myeloid leukemia cells. Int J Cancer 123:217–226

    CAS  PubMed  Google Scholar 

  169. Ta HQ, Thomas KS, Schrecengost RS, Bouton AH (2008) A novel association between p130Cas and resistance to the chemotherapeutic drug adriamycin in human breast cancer cells. Cancer Res 68:8796–8804

    CAS  PubMed  Google Scholar 

  170. Hakak Y, Martin GS (1999) Cas mediates transcriptional activation of the serum response element by Src. Mol Cell Biol 19:6953–6962

    CAS  PubMed  Google Scholar 

  171. Pylayeva Y, Gillen KM, Gerald W, Beggs HE, Reichardt LF, Giancotti FG (2009) Ras- and PI3 K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling. J Clin Invest 119:252–266

    CAS  PubMed  Google Scholar 

  172. Dorssers LC, van Agthoven T, Brinkman A, Veldscholte J, Smid M, Dechering KJ (2005) Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway. Breast Cancer Res 7:R82–R92

    CAS  PubMed  Google Scholar 

  173. Izumchenko E, Singh MK, Plotnikova OV, Tikhmyanova N, Little JL, Serebriiskii IG, Seo S, Kurokawa M, Egleston BL, Klein-Szanto A, Pugacheva EN, Hardy RR, Wolfson M, Connolly DC, Golemis EA (2009) NEDD9 promotes oncogenic signaling in mammary tumor development. Cancer Res 69:7198–7206

    CAS  PubMed  Google Scholar 

  174. Cabodi S, Moro L, Baj G, Smeriglio M, Di Stefano P, Gippone S, Surico N, Silengo L, Turco E, Tarone G, Defilippi P (2004) p130Cas interacts with estrogen receptor alpha and modulates non-genomic estrogen signaling in breast cancer cells. J Cell Sci 117:1603–1611

    CAS  PubMed  Google Scholar 

  175. Kim W, Seok Kang Y, Soo Kim J, Shin NY, Hanks SK, Song WK (2008) The integrin-coupled signaling adaptor p130Cas suppresses Smad3 function in transforming growth factor-beta signaling. Mol Biol Cell 19:2135–2146

    CAS  PubMed  Google Scholar 

  176. Marumoto T, Zhang D, Saya H (2005) Aurora-A - a guardian of poles. Nat Rev Cancer 5:42–50

    CAS  PubMed  Google Scholar 

  177. Honda K, Mihara H, Kato Y, Yamaguchi A, Tanaka H, Yasuda H, Furukawa K, Urano T (2000) Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway. Oncogene 19:2812–2819

    CAS  PubMed  Google Scholar 

  178. Zhou H, Kuang J, Zhong L, Kuo WL, Gray JW, Sahin A, Brinkley BR, Sen S (1998) Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet 20:189–193

    CAS  PubMed  Google Scholar 

  179. Pugacheva EN, Golemis EA (2006) HEF1-aurora A interactions: points of dialog between the cell cycle and cell attachment signaling networks. Cell Cycle 5:384–391

    CAS  PubMed  Google Scholar 

  180. Fritz G, Kaina B (2006) Rho GTPases: promising cellular targets for novel anticancer drugs. Curr Cancer Drug Targets 6:1–14

    CAS  PubMed  Google Scholar 

  181. Glotzer M (2003) Cytokinesis: progress on all fronts. Curr Opin Cell Biol 15:684–690

    CAS  PubMed  Google Scholar 

  182. Singla V, Reiter JF (2006) The primary cilium as the cell’s antenna: signaling at a sensory organelle. Science 313:629–633

    CAS  PubMed  Google Scholar 

  183. Plotnikova OV, Golemis EA, Pugacheva EN (2008) Cell cycle-dependent ciliogenesis and cancer. Cancer Res 68:2058–2061

    CAS  PubMed  Google Scholar 

  184. Roodman GD (1996) Advances in bone biology: the osteoclast. Endocr Rev 17:308–332

    CAS  PubMed  Google Scholar 

  185. Duong LT, Lakkakorpi PT, Nakamura I, Machwate M, Nagy RM, Rodan GA (1998) PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of alpha(v)beta3 integrin, and phosphorylated by src kinase. J Clin Invest 102:881–892

    CAS  PubMed  Google Scholar 

  186. Lakkakorpi PT, Nakamura I, Nagy RM, Parsons JT, Rodan GA, Duong LT (1999) Stable association of PYK2 and p130(Cas) in osteoclasts and their co-localization in the sealing zone. J Biol Chem 274:4900–4907

    CAS  PubMed  Google Scholar 

  187. Nakamura I, Kadono Y, Takayanagi H, Jimi E, Miyazaki T, Oda H, Nakamura K, Tanaka S, Rodan GA, Duong le T (2002) IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor-associated factor 6/c-Src complex. J Immunol 168:5103–5109

    CAS  PubMed  Google Scholar 

  188. Duong LT, Nakamura I, Lakkakorpi PT, Lipfert L, Bett AJ, Rodan GA (2001) Inhibition of osteoclast function by adenovirus expressing antisense protein-tyrosine kinase 2. J Biol Chem 276:7484–7492

    CAS  PubMed  Google Scholar 

  189. Chellaiah MA, Biswas RS, Yuen D, Alvarez UM, Hruska KA (2001) Phosphatidylinositol 3, 4, 5-trisphosphate directs association of Src homology 2-containing signaling proteins with gelsolin. J Biol Chem 276:47434–47444

    CAS  PubMed  Google Scholar 

  190. Zhang Z, Neff L, Bothwell AL, Baron R, Horne WC (2002) Calcitonin induces dephosphorylation of Pyk2 and phosphorylation of focal adhesion kinase in osteoclasts. Bone 31:359–365

    CAS  PubMed  Google Scholar 

  191. Weidow CL, Black DS, Bliska JB, Bouton AH (2000) CAS/Crk signalling mediates uptake of Yersinia into human epithelial cells. Cell Microbiol 2:549–560

    CAS  PubMed  Google Scholar 

  192. Shi J, Casanova JE (2006) Invasion of host cells by Salmonella typhimurium requires focal adhesion kinase and p130Cas. Mol Biol Cell 17:4698–4708

    CAS  PubMed  Google Scholar 

  193. Halle M, Gomez MA, Stuible M, Shimizu H, McMaster WR, Olivier M, Tremblay ML (2009) The Leishmania surface protease GP63 cleaves multiple intracellular proteins and actively participates in p38 mitogen-activated protein kinase inactivation. J Biol Chem 284:6893–6908

    CAS  PubMed  Google Scholar 

  194. Gower TL, Peeples ME, Collins PL, Graham BS (2001) RhoA is activated during respiratory syncytial virus infection. Virology 283:188–196

    CAS  PubMed  Google Scholar 

  195. Li E, Stupack DG, Brown SL, Klemke R, Schlaepfer DD, Nemerow GR (2000) Association of p130CAS with phosphatidylinositol-3-OH kinase mediates adenovirus cell entry. J Biol Chem 275:14729–14735

    CAS  PubMed  Google Scholar 

  196. Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T (1995) Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377:539–544

    CAS  PubMed  Google Scholar 

  197. Kovacic-Milivojevic B, Damsky CC, Gardner DG, Ilic D (2002) Requirements for the localization of p130 Cas to Z-lines in cardiac myocytes. Cell Mol Biol Lett 7:323–329

    CAS  PubMed  Google Scholar 

  198. Beaty TH, Fallin MD, Hetmanski JB, McIntosh I, Chong SS, Ingersoll R, Sheng X, Chakraborty R, Scott AF (2005) Haplotype diversity in 11 candidate genes across four populations. Genetics 171:259–267

    CAS  PubMed  Google Scholar 

  199. Toriello HV (2009) Are the oral-facial-digital syndromes ciliopathies? Am J Med Genet A 149A:1089–1095

    PubMed  Google Scholar 

  200. Huang Z, Yazdani U, Thompson-Peer KL, Kolodkin AL, Terman JR (2007) Crk-associated substrate (Cas) signaling protein functions with integrins to specify axon guidance during development. Development 134:2337–2347

    CAS  PubMed  Google Scholar 

  201. Burnham MR, Harte MT, Richardson A, Parsons JT, Bouton AH (1996) The identification of p130cas-binding proteins and their role in cellular transformation. Oncogene 12:2467–2472

    CAS  PubMed  Google Scholar 

  202. Iwahara T, Akagi T, Fujitsuka Y, Hanafusa H (2004) CrkII regulates focal adhesion kinase activation by making a complex with Crk-associated substrate, p130Cas. Proc Natl Acad Sci USA 101:17693–17698

    CAS  PubMed  Google Scholar 

  203. Sakai R, Nakamoto T, Ozawa K, Aizawa S, Hirai H (1997) Characterization of the kinase activity essential for tyrosine phosphorylation of p130Cas in fibroblasts. Oncogene 14:1419–1426

    CAS  PubMed  Google Scholar 

  204. Auvinen M, Paasinen-Sohns A, Hirai H, Andersson LC, Holtta E (1995) Ornithine decarboxylase- and ras-induced cell transformations: reversal by protein tyrosine kinase inhibitors and role of pp130CAS. Mol Cell Biol 15:6513–6525

    CAS  PubMed  Google Scholar 

  205. de Cremoux P, Tran-Perennou C, Brockdorff BL, Boudou E, Brunner N, Magdelenat H, Lykkesfeldt AE (2003) Validation of real-time RT-PCR for analysis of human breast cancer cell lines resistant or sensitive to treatment with antiestrogens. Endocr Relat Cancer 10:409–418

    PubMed  Google Scholar 

  206. Dorssers LC, Grebenchtchikov N, Brinkman A, Look MP, van Broekhoven SP, de Jong D, Peters HA, Portengen H, Meijer-van Gelder ME, Klijn JG, van Tienoven DT, Geurts-Moespot A, Span PN, Foekens JA, Sweep FC (2004) The prognostic value of BCAR1 in patients with primary breast cancer. Clin Cancer Res 10:6194–6202

    CAS  PubMed  Google Scholar 

  207. Near RI, Zhang Y, Makkinje A, Vanden Borre P, Lerner A (2007) AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology. J Cell Physiol 212:655–665

    CAS  PubMed  Google Scholar 

  208. Schrecengost RS, Riggins RB, Thomas KS, Guerrero MS, Bouton AH (2007) Breast cancer antiestrogen resistance-3 expression regulates breast cancer cell migration through promotion of p130Cas membrane localization and membrane ruffling. Cancer Res 67:6174–6182

    CAS  PubMed  Google Scholar 

  209. Soni S, Lin BT, August A, Nicholson RI, Kirsch KH (2009) Expression of a phosphorylated p130(Cas) substrate domain attenuates the phosphatidylinositol 3-kinase/Akt survival pathway in tamoxifen resistant breast cancer cells. J Cell Biochem 107:364–375

    CAS  PubMed  Google Scholar 

  210. van Agthoven T, Sieuwerts AM, Meijer-van Gelder ME, Look MP, Smid M, Veldscholte J, Sleijfer S, Foekens JA, Dorssers LC (2009) Relevance of breast cancer antiestrogen resistance genes in human breast cancer progression and tamoxifen resistance. J Clin Oncol 27:542–549

    PubMed  Google Scholar 

  211. Konstantinovsky S, Smith Y, Zilber S, Tuft Stavnes H, Becker AM, Nesland JM, Reich R, Davidson B (2010) Breast carcinoma cells in primary tumors and effusions have different gene array profiles. J Oncol 2010:969084

    PubMed  Google Scholar 

  212. Scibelli A, d’Angelo D, Pelagalli A, Tafuri S, Avallone L, Della Morte R, Staiano N (2003) Expression levels of the focal adhesion-associated proteins paxillin and p130CAS in canine and feline mammary tumors. Vet Res 34:193–202

    CAS  PubMed  Google Scholar 

  213. Spencer KS, Graus-Porta D, Leng J, Hynes NE, Klemke RL (2000) ErbB2 is necessary for induction of carcinoma cell invasion by ErbB family receptor tyrosine kinases. J Cell Biol 148:385–397

    CAS  PubMed  Google Scholar 

  214. Riggins RB, Quilliam LA, Bouton AH (2003) Synergistic promotion of c-Src activation and cell migration by Cas and AND-34/BCAR3. J Biol Chem 278:28264–28273

    CAS  PubMed  Google Scholar 

  215. Vultur A, Buettner R, Kowolik C, Liang W, Smith D, Boschelli F, Jove R (2008) SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. Mol Cancer Ther 7:1185–1194

    CAS  PubMed  Google Scholar 

  216. Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massague J (2005) Genes that mediate breast cancer metastasis to lung. Nature 436:518–524

    CAS  PubMed  Google Scholar 

  217. Nagashima T, Oyama M, Kozuka-Hata H, Yumoto N, Sakaki Y, Hatakeyama M (2008) Phosphoproteome and transcriptome analyses of ErbB ligand-stimulated MCF-7 cells. Cancer Genomics Proteomics 5:161–168

    CAS  PubMed  Google Scholar 

  218. Giampieri S, Manning C, Hooper S, Jones L, Hill CS, Sahai E (2009) Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility. Nat Cell Biol (in press)

  219. Tamura M, Gu J, Takino T, Yamada KM (1999) Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130Cas. Cancer Res 59:442–449

    CAS  PubMed  Google Scholar 

  220. Frankel P, Pellet-Many C, Lehtolainen P, D’Abaco GM, Tickner ML, Cheng L, Zachary IC (2008) Chondroitin sulphate-modified neuropilin 1 is expressed in human tumour cells and modulates 3D invasion in the U87MG human glioblastoma cell line through a p130Cas-mediated pathway. EMBO Rep 9:983–989

    CAS  PubMed  Google Scholar 

  221. Seo S, Ichikawa M, Kurokawa M (2006) Structure and function of cas-L and integrin-mediated signaling. Crit Rev Immunol 26:391–406

    CAS  PubMed  Google Scholar 

  222. Iwata S, Kobayashi H, Miyake-Nishijima R, Sasaki T, Souta-Kuribara A, Nori M, Hosono O, Kawasaki H, Tanaka H, Morimoto C (2002) Distinctive signaling pathways through CD82 and beta1 integrins in human T cells. Eur J Immunol 32:1328–1337

    CAS  PubMed  Google Scholar 

  223. de Jong R, van Wijk A, Haataja L, Heisterkamp N, Groffen J (1997) BCR/ABL-induced leukemogenesis causes phosphorylation of Hef1 and its association with Crkl. J Biol Chem 272:32649–32655

    PubMed  Google Scholar 

  224. Cho YJ, Hemmeryckx B, Groffen J, Heisterkamp N (2005) Interaction of Bcr/Abl with C3G, an exchange factor for the small GTPase Rap1, through the adapter protein Crkl. Biochem Biophys Res Commun 333:1276–1283

    CAS  PubMed  Google Scholar 

  225. Ambrogio C, Voena C, Manazza AD, Piva R, Riera L, Barberis L, Costa C, Tarone G, Defilippi P, Hirsch E, Boeri Erba E, Mohammed S, Jensen ON, Palestro G, Inghirami G, Chiarle R (2005) p130Cas mediates the transforming properties of the anaplastic lymphoma kinase. Blood 106:3907–3916

    CAS  PubMed  Google Scholar 

  226. Petti F, Thelemann A, Kahler J, McCormack S, Castaldo L, Hunt T, Nuwaysir L, Zeiske L, Haack H, Sullivan L, Garton A, Haley JD (2005) Temporal quantitation of mutant Kit tyrosine kinase signaling attenuated by a novel thiophene kinase inhibitor OSI-930. Mol Cancer Ther 4:1186–1197

    CAS  PubMed  Google Scholar 

  227. Moore SR, Persons DL, Sosman JA, Bobadilla D, Bedell V, Smith DD, Wolman SR, Tuthill RJ, Moon J, Sondak VK, Slovak ML (2008) Detection of copy number alterations in metastatic melanoma by a DNA fluorescence in situ hybridization probe panel and array comparative genomic hybridization: a southwest oncology group study (S9431). Clin Cancer Res 14:2927–2935

    CAS  PubMed  Google Scholar 

  228. Sanz-Moreno V, Gadea G, Ahn J, Paterson H, Marra P, Pinner S, Sahai E, Marshall CJ (2008) Rac activation and inactivation control plasticity of tumor cell movement. Cell 135:510–523

    CAS  PubMed  Google Scholar 

  229. Eisenmann KM, McCarthy JB, Simpson MA, Keely PJ, Guan JL, Tachibana K, Lim L, Manser E, Furcht LT, Iida J (1999) Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas. Nat Cell Biol 1:507–513

    CAS  PubMed  Google Scholar 

  230. Chang CC, Campoli M, Luo W, Zhao W, Zaenker KS, Ferrone S (2004) Immunotherapy of melanoma targeting human high molecular weight melanoma-associated antigen: potential role of nonimmunological mechanisms. Ann N Y Acad Sci 1028:340–350

    CAS  PubMed  Google Scholar 

  231. Hamamura K, Furukawa K, Hayashi T, Hattori T, Nakano J, Nakashima H, Okuda T, Mizutani H, Hattori H, Ueda M, Urano T, Lloyd KO (2005) Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells. Proc Natl Acad Sci USA 102:11041–11046

    CAS  PubMed  Google Scholar 

  232. Hamamura K, Tsuji M, Ohkawa Y, Nakashima H, Miyazaki S, Urano T, Yamamoto N, Ueda M, Furukawa K (2008) Focal adhesion kinase as well as p130Cas and paxillin is crucially involved in the enhanced malignant properties under expression of ganglioside GD3 in melanoma cells. Biochim Biophys Acta 1780:513–519

    CAS  PubMed  Google Scholar 

  233. Ohkawa Y, Miyazaki S, Miyata M, Hamamura K, Furukawa K (2008) Essential roles of integrin-mediated signaling for the enhancement of malignant properties of melanomas based on the expression of GD3. Biochem Biophys Res Commun 373:14–19

    CAS  PubMed  Google Scholar 

  234. Nakashima H, Hamamura K, Houjou T, Taguchi R, Yamamoto N, Mitsudo K, Tohnai I, Ueda M, Urano T, Furukawa K (2007) Overexpression of caveolin-1 in a human melanoma cell line results in dispersion of ganglioside GD3 from lipid rafts and alteration of leading edges, leading to attenuation of malignant properties. Cancer Sci 98:512–520

    CAS  PubMed  Google Scholar 

  235. Fromont G, Vallancien G, Validire P, Levillain P, Cussenot O (2007) BCAR1 expression in prostate cancer: association with 16q23 LOH status, tumor progression and EGFR/KAI1 staining. Prostate 67:268–273

    PubMed  Google Scholar 

  236. Zhang XA, He B, Zhou B, Liu L (2003) Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration. J Biol Chem 278:27319–27328

    CAS  PubMed  Google Scholar 

  237. Guo C, Liu QG, Yang W, Zhang ZL, Yao YM (2008) Relation among p130Cas, E-cadherin and beta-catenin expression, clinicopathologic significance and prognosis in human hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 7:490–496

    PubMed  Google Scholar 

  238. Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, Liang MC, Cai D, Naumov GN, Bao L, Contreras CM, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Lindeman NI, Christiani DC, Lin X, Shapiro GI, Janne PA, Johnson BE, Meyerson M, Kwiatkowski DJ, Castrillon DH, Bardeesy N, Sharpless NE, Wong KK (2007) LKB1 modulates lung cancer differentiation and metastasis. Nature 448:807–810

    CAS  PubMed  Google Scholar 

  239. Zhang PJ, Weber R, Liang HH, Pasha TL, LiVolsi VA (2003) Growth factors and receptors in juvenile nasopharyngeal angiofibroma and nasal polyps: an immunohistochemical study. Arch Pathol Lab Med 127:1480–1484

    CAS  PubMed  Google Scholar 

  240. Casanova I, Parreno M, Farre L, Guerrero S, Cespedes MV, Pavon MA, Sancho FJ, Marcuello E, Trias M, Mangues R (2006) Celecoxib induces anoikis in human colon carcinoma cells associated with the deregulation of focal adhesions and nuclear translocation of p130Cas. Int J Cancer 118:2381–2389

    CAS  PubMed  Google Scholar 

  241. Seidl C, Port M, Apostolidis C, Bruchertseifer F, Schwaiger M, Senekowitsch-Schmidtke R, Abend M (2009) Differential gene expression triggered by highly cytotoxic alpha-Emitter-immunoconjugates in gastric cancer cells. Invest New Drugs (in press)

  242. Beinke C, Van Beuningen D, Cordes N (2003) Ionizing radiation modules of the expression and tyrosine phosphorylation of the focal adhesion-associated proteins focal adhesion kinase (FAK) and its substrates p130cas and paxillin in A549 human lung carcinoma cells in vitro. Int J Radiat Biol 79:721–731

    CAS  PubMed  Google Scholar 

  243. Seidler J, Durzok R, Brakebusch C, Cordes N (2005) Interactions of the integrin subunit beta1A with protein kinase B/Akt, p130Cas and paxillin contribute to regulation of radiation survival. Radiother Oncol 76:129–134

    CAS  PubMed  Google Scholar 

  244. Miyake-Nishijima R, Iwata S, Saijo S, Kobayashi H, Kobayashi S, Souta-Kuribara A, Hosono O, Kawasaki H, Tanaka H, Ikeda E, Okada Y, Iwakura Y, Morimoto C (2003) Role of Crk-associated substrate lymphocyte type in the pathophysiology of rheumatoid arthritis in tax transgenic mice and in humans. Arthritis Rheum 48:1890–1900

    CAS  PubMed  Google Scholar 

  245. Chapuis J, Moisan F, Mellick G, Elbaz A, Silburn P, Pasquier F, Hannequin D, Lendon C, Campion D, Amouyel P, Lambert JC (2008) Association study of the NEDD9 gene with the risk of developing Alzheimer’s and Parkinson’s disease. Hum Mol Genet 17:2863–2867

    CAS  PubMed  Google Scholar 

  246. Li Y, Grupe A, Rowland C, Holmans P, Segurado R, Abraham R, Jones L, Catanese J, Ross D, Mayo K, Martinez M, Hollingworth P, Goate A, Cairns NJ, Racette BA, Perlmutter JS, O’Donovan MC, Morris JC, Brayne C, Rubinsztein DC, Lovestone S, Thal LJ, Owen MJ, Williams J (2008) Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer’s and Parkinson’s disease. Hum Mol Genet 17:759–767

    CAS  PubMed  Google Scholar 

  247. Chouery E, Delague V, Bergougnoux A, Koussa S, Serre JL, Megarbane A (2008) Mutations in TREM2 lead to pure early-onset dementia without bone cysts. Hum Mutat 29:E194–E204

    PubMed  Google Scholar 

  248. Singh M, Cowell L, Seo S, O’Neill G, Golemis E (2007) Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional co-ordinator of invasion, apoptosis and cell cycle. Cell Biochem Biophys 48:54–72

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Dr. Mark Andrake of the Fox Chase Cancer Center Molecular Modeling Facility for help in producing Fig. 1a. N.T. and E.A.G. were supported by NIH R01 CA63366 and R01 CA113342, and by Pennsylvania Tobacco Settlement funding (to E.A.G.); J.L.L. was supported by NIH T32 CA009035; and all authors by NIH core grant CA06927 and a gift from the Pew Charitable Trust (to Fox Chase Cancer Center).

Author information

Authors and Affiliations

  1. Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA, 19111, USA

    Nadezhda Tikhmyanova, Joy L. Little & Erica A. Golemis

  2. Department of Biochemistry, Drexel University Medical School, Philadelphia, PA, 19102, USA

    Nadezhda Tikhmyanova

Authors
  1. Nadezhda Tikhmyanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joy L. Little
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erica A. Golemis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erica A. Golemis.

Additional information

N. Tikhmyanova and J. L. Little have contributed equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tikhmyanova, N., Little, J.L. & Golemis, E.A. CAS proteins in normal and pathological cell growth control. Cell. Mol. Life Sci. 67, 1025–1048 (2010). https://doi.org/10.1007/s00018-009-0213-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-009-0213-1

Keywords

Search

Navigation