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Functions of the adapter protein Cas: signal convergence and the determination of cellular responses

Abstract

Since Cas was first identified as a highly phosphorylated 130 kilodalton protein that associated with the v-Src and v-Crk-oncoproteins, considerable effort has been made to determine its function. Its predicted role as a scaffolding molecule based on its domain structure has been largely confirmed. Through its ability to undergo rapid changes in phosphorylation, subcellular localization and association with heterologous proteins, Cas may spatially and temporally regulate the function of its binding partners. Numerous proteins have been identified that bind to Cas in vitro and/or in vivo, but in only a few cases is there an understanding of how Cas may function in these protein complexes. To date, Cas-Crk and Cas-Src complexes have been most frequently implicated in Cas function, particularly in regards to processes involving regulation of the actin cytoskeleton and proliferation. These and other Cas protein complexes contribute to the critical role of Cas in cell adhesion, migration, proliferation and survival of normal cycling cells. However, under conditions in which these processes are deregulated, Cas appears to play a role in oncogenic transformation and perhaps metastasis. Therefore, in its capacity as an adapter protein, Cas serves as a point of convergence for many distinct signaling inputs, ultimately contributing to the generation of specific cellular responses.

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References

  • Alexandropoulos K, Baltimore D . 1996 Gene Dev. 10: 1341–1355

  • Almeida EA, Ilic D, Han Q, Hauck CR, Jin F, Kawakatsu H, Schlaepfer DD, Damsky CH . 2000 J. Cell. Biol. 149: 741–754

  • Andersson K, Carballeira N, Magnusson KE, Persson C, Stendahl O, Wolf-Watz H, Fallman M . 1996 Mol. Microbiol. 20: 1057–1069

  • Aplin AE, Juliano RL . 1999 J. Cell. Sci. 112: 695–706

  • Arai A, Nosaka Y, Kohsaka H, Miyasaka N, Miura O . 1999 Blood 93: 3713–3722

  • Astier A, Manie SN, Avraham H, Hirai H, Law SF, Zhang YH, Golemis EA, Fu YG, Druker BJ, Haghayeghi N, Freedman AS, Avraham S . 1997a J. Biol. Chem. 272: 19719–19724

  • Astier A, Manie SN, Law SF, Canty T, Haghayghi N, Druker BJ, Salgia R, Golemis EA, Freedman AS . 1997b Leuk. Lymph. 28: 65–72

  • Auvinen M, Paasinen-Sohns A, Hirai H, Andersson LC, Holtta E . 1995 Mol. Cell. Biol. 15: 6513–6525

  • Bannerman DD, Sathyamoorthy M, Goldblum SE . 1998 J. Biol. Chem. 273: 35371–35380

  • Biscardi JS, Belsches AP, Parsons SJ . 1998 Mol. Carcinogen. 21: 261–272

  • Black DS, Bliska JB . 1997 EMBO J. 16: 2730–2744

  • Black DS, Montagna LG, Zitsmann S, Bliska JB . 1998 Mol. Microbiol. 29: 1263–1274

  • Brinkman A, van der Flier S, Kok EM, Dorssers LC . 2000 J. Natl. Cancer Inst. 92: 112–120

  • Bruce-Staskal PJ, Bouton AH . 2001 Exp. Cell. Res. 264: 296–306

  • Burnham MR, Bruce-Staskal PJ, Harte MT, Weidow CL, Ma A, Weed SA, Bouton AH . 2000 Mol. Cell. Biol. 20: 5865–5878

  • Burnham MR, Harte MT, Bouton AH . 1999 Mol. Carcinogen. 26: 20–31

  • Burnham MR, Harte MT, Richardson A, Parsons JT, Bouton AH . 1996 Oncogene 12: 2467–2472

  • Cai DP, Clayton LK, Smolyar A, Lerner A . 1999 J. Immunol. 163: 2104–2112

  • Cary LA, Chang JF, Guan JL . 1996 J. Cell. Sci. 109: 1787–1794

  • Cary LA, Han DC, Polte TR, Hanks SK, Guan JL . 1998 J. Cell. Biol. 140: 211–221

  • Casamassima A, Rozengurt E . 1997 J. Biol. Chem. 272: 9363–9370

  • Casamassima A, Rozengurt E . 1998 J. Biol. Chem. 273: 26149–26156

  • Chan PC, Lai JF, Cheng CH, Tang MJ, Chiu CC, Chen HC . 1999 J. Biol. Chem. 274: 26901–26906

  • Chan YR, Gallo RL . 1998 J. Biol. Chem. 273: 28978–28985

  • Cheresh DA, Leng J, Klemke RL . 1999 J. Cell. Biol. 146: 1107–1116

  • Cho SY, Klemke RL . 2000 J. Cell. Biol. 149: 223–236

  • Critchley DR . 2000 Curr. Opin. Cell. Biol. 12: 133–139

  • Dejong R, Vanwijk A, Haataja L, Heisterkamp N, Groffen J . 1997 J. Biol. Chem. 272: 32649–32655

  • Dersch P, Isberg RR . 2000 Infect. Immun. 68: 2930–2938

  • Dodelet VC, Pazzagli C, Zisch AH, Hauser CA, Pasquale EB . 1999 J. Biol. Chem. 274: 31941–31946

  • Dolfi F, Garcia-Guzman M, Ojaniemi M, Nakamura H, Matsuda M, Vuori K . 1998 Proc. Natl. Acad. Sci. USA 95: 15394–15399

  • Donaldson JC, Dempsey PJ, Reddy S, Bouton AH, Coffey RJ, Hanks SK . 2000 Exp. Cell. Res. 256: 168–178

  • Eisenmann KM, McCarthy JB, Simpson MA, Keely PJ, Guan JL, Tachibana K, Lim L, Manser E, Furcht LT, Iida J . 1999 Nat. Cell. Biol. 1: 507–513

  • Ferris HA, Tapia JA, Garcia LJ, Jensen RT . 1999 Biochem. 38: 1497–1508

  • Foekens JA, Schmitt M, van Putten WL, Peters HA, Kramer MD, Janicke F, Klijn JG . 1994 J. Clin. Oncol. 12: 1648–1658

  • Frisch SM, Ruoslahti E . 1997 Curr. Opin. Cell. Biol. 9: 701–706

  • Frischknecht F, Way M . 2001 Trends Cell. Biol. 11: 30–38

  • Garcia-Guzman M, Dolfi F, Russello M, Vuori K . 1999 J. Biol. Chem. 274: 5762–5768

  • Garton AJ, Flint AJ, Tonks NK . 1996 Mol. Cell. Biol. 16: 6408–6418

  • Garton AJ, Tonks NK . 1999 J. Biol. Chem. 274: 3811–3818

  • George EL, Georges-Labouesse EN, Patel-King RS, Rayburn H, Hynes RO . 1993 Development 119: 1079–1091

  • Giancotti FG . 1997 Curr. Opin. Cell. Biol. 9: 691–700

  • Gotoh T, Cai D, Tian X, Feig LA, Lerner A . 2000 J. Biol. Chem. 275: 30118–30123

  • Hakak Y, Martin GS . 1999 Mol. Cell. Biol. 19: 6953–6962

  • Hamasaki K, Mimura T, Morino N, Furuya H, Nakamoto T, Aizawa SI, Morimoto C, Yazaki Y, Hirai H, Nojima Y . 1996 Biochem. Biophys. Res. Commun. 222: 338–343

  • Harrington EO, Smeglin A, Newton J, Ballard G, Rounds S . 2001 Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L342–L353

  • Harte MT, Hildebrand JD, Burnham MR, Bouton AH, Parsons JT . 1996 J. Biol. Chem. 271: 13649–13655

  • Harte MT, Macklem M, Weidow CL, Parsons JT, Bouton AH . 2000 Biochim. Biophys. Acta 1499: 34–48

  • Honda H, Nakamoto T, Sakai R, Hirai H . 1999 Biochem. Biophys. Res. Commun. 262: 25–30

  • 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 Nat. Gen. 19: 361–365

  • Howe A, Aplin AE, Alahari SK, Juliano RL . 1998 Curr. Opin. Cell. Biol. 10: 220–231

  • Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T . 1995 Nature 377: 539–544

  • Isberg RR, Hamburger Z, Dersch P . 2000 Microb. Infect. 2: 793–801

  • Ishino M, Ohba T, Sasaki H, Sasaki T . 1995 Oncogene 11: 2331–2338

  • Jove R, Hanafusa H . 1987 Annu. Rev. Cell. Biol. 3: 31–56

  • Kanner SB, Reynolds AB, Wang HC, Vines RR, Parsons JT . 1991 EMBO J. 10: 1689–1698

  • Khwaja A, Hallberg B, Warne PH, Downward J . 1996 Oncogene 12: 2491–2498

  • Kirsch KH, Georgescu MM, Hanafusa H . 1998 J. Biol. Chem. 273: 25673–25679

  • Kirsch KH, Georgescu MM, Ishimaru S, Hanfusa H . 1999 Proc. Natl. Acad. Sci. USA 96: 6211–6216

  • Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M . 1998a Gene. Dev. 12: 3331–3336

  • Kiyokawa E, Hashimoto Y, Kurata T, Sugimura H, Matsuda M . 1998b J. Biol. Chem. 273: 24479–24484

  • Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA . 1998 J. Cell. Biol. 140: 961–972

  • Klinghoffer RA, Sachsenmaier C, Cooper JA, Soriano P . 1999 EMBO J. 18: 2459–2471

  • Kook S, Shim SR, Choi SJ, Ahnn J, Kim JI, Eom SH, Jung YK, Paik SG, Song WK . 2000a Mol. Biol. Cell. 11: 929–939

  • Kook S, Shim SR, Kim JI, Ahnn JH, Jung YK, Paik SG, Song WK . 2000b Cel. Biochem. Funct. 18: 1–7

  • Koster A, Landgraf S, Leipold A, Sachse R, Gebhart E, Tulusan AH, Ronay G, Schmidt C, Dingermann T . 1991 Anticancer Res. 11: 193–201

  • Lakkakorpi PT, Nakamura I, Nagy RM, Parsons JT, Rodan GA, Duong LT . 1999 J. Biol. Chem. 274: 4900–4907

  • Lamorte L, Kamikura DM, Park M . 2000 Oncogene 19: 5973–5981

  • Larsson H, Klint P, Landgren E, Claesson-Welsh L . 1999 J. Biol. Chem. 274: 25726–25734

  • Law SF, Estojak J, Wang BL, Mysliwiec T, Kruh G, Golemis EA . 1996 Mol. Cell. Biol. 16: 3327–3337

  • Law SF, O'Neill GM, Fashena SJ, Einarson MB, Golemis EA . 2000 Mol. Cell. Biol. 20: 5184–5195

  • Law SF, Zhang YZ, Fashena SJ, Toby G, Estojak J, Golemis EA . 1999 Exp. Cell. Res. 252: 224–235

  • Law SF, Zhang YZ, Kleinszanto AJP, Golemis EA . 1998 Mol. Cell. Biol. 18: 3540–3551

  • Li E, Stupack DG, Brown SL, Klemke R, Schlaepfer DD, Nemerow GR . 2000 J. Biol. Chem. 275: 14729–14735

  • Liu F, Hill DE, Chernoff J . 1996 J. Biol. Chem. 271: 31290–31295

  • Lu YM, Brush J, Stewart TA . 1999 J. Biol. Chem. 274: 10047–10052

  • Matsuda M, Mayer BJ, Fukui Y, Hanafusa H . 1990 Science 248: 1537–1539

  • Matsuda M, Mayer BJ, Hanafusa H . 1991 Mol. Cell. Biol. 11: 1607–1613

  • Matsuda M, Ota S, Tanimura R, Nakamura H, Matuoka K, Takenawa T, Nagashima K, Kurata T . 1996 J. Biol. Chem. 271: 14468–14472

  • Mayer BJ, Hamaguchi M, Hanafusa H . 1988 Cold Spring Harb. Symp. Quant. Biol. 53: 907–914

  • Mayer BJ, Hanafusa H . 1990a Proc. Natl. Acad. Sci. USA 87: 2638–2642

  • Mayer BJ, Hanafusa H . 1990b J. Virol. 64: 3581–3589

  • Mayer BJ, Hirai H, Sakai R . 1995 Curr. Biol. 5: 296–305

  • Meijne AM, Ruuls-Van Stalle L, Feltkamp CA, McCarthy JB, Roos E . 1997 Exp. Cell. Res. 234: 477–485

  • Mielenz D, Hapke S, Poschl E, von Der Mark H, von Der Mark K . 2001 J. Biol. Chem. 276: 13417–13426

  • Minegishi M, Tachibana K, Sato T, Iwata S, Nojima Y, Morimoto C . 1996 J. Exp. Med. 184: 1365–1375

  • Murakami H, Iwashita T, Asai N, Iwata Y, Narumiya S, Takahashi M . 1999 Oncogene 18: 1975–1982

  • Nakamoto T, Sakai R, Honda H, Ogawa S, Ueno H, Suzuki T, Aizawa S, Yazaki Y, Hirai H . 1997 Mol. Cell. Biol. 17: 3884–3897

  • Nakamoto T, Sakai R, Ozawa K, Yazaki Y, Hirai H . 1996 J. Biol. Chem. 271: 8959–8965

  • Nakamoto T, Yamagata T, Sakai R, Ogawa S, Honda H, Ueno H, Hirano N, Yazaki Y, Hirai H . 2000 Mol. Cell. Biol. 20: 1649–1658

  • Nakamura I, Jimi E, Duong LT, Sasaki T, Takahashi N, Rodan GA, Suda T . 1998 J. Biol. Chem. 273: 11144–11149

  • Needham LK, Rozengurt E . 1998 J. Biol. Chem. 273: 14626–14632

  • Nojima Y, Morino N, Mimura T, Hamasaki K, Furuya H, Sakai R, Sato T, Tachibana K, Morimoto C, Yazaki Y, Hirai H . 1995 J. Biol. Chem. 270: 15398–15402

  • Ojaniemi M, Vuori K . 1997 J. Biol. Chem. 272: 25993–25998

  • Oktay M, Wary KK, Dans M, Birge RB, Giancotti FG . 1999 J. Cell. Biol. 145: 1461–1469

  • O'Neill GM, Fashena SJ, Golemis EA . 2000 Trends Cell. Biol. 10: 111–119

  • Owen JD, Ruest PJ, Fry DW, Hanks SK . 1999 Mol. Cell. Biol. 19: 4806–4818

  • Persson C, Carballeira N, Wolf-Watz H, Fallman M . 1997 EMBO J. 16: 2307–2318

  • Petch LA, Bockholt SM, Bouton A, Parsons JT, Burridge K . 1995 J. Cell. Sci. 108: 1371–1379

  • Polte TR, Hanks SK . 1995 Proc. Natl. Acad. Sci. USA 92: 10678–10682

  • Polte TR, Hanks SK . 1997 J. Biol. Chem. 272: 5501–5509

  • Prasad N, Topping RS, Decker SJ . 2001 Mol. Cell. Biol. 21: 1416–1428

  • Reiske HR, Zhao J, Han DC, Cooper LA, Guan JL . 2000 FEBS Lett. 486: 275–280

  • Reynolds AB, Kanner SB, Wang HC, Parsons JT . 1989 Mol. Cell. Biol. 9: 3951–3958

  • Ribon V, Saltiel AR . 1996 J. Biol. Chem. 271: 7375–7380

  • Sakai R, Iwamatsu A, Hirano N, Ogawa S, Tanaka T, Mano H, Yazaki Y, Hirai H . 1994a EMBO J. 13: 3748–3756

  • Sakai R, Iwamatsu A, Hirano N, Ogawa S, Tanaka T, Nishida J, Yazaki Y, Hirai H . 1994b J. Biol. Chem. 269: 32740–32746

  • Sakakibara A, Hattori S . 2000 J. Biol. Chem. 275: 6404–6410

  • Salgia R, Pisick E, Sattler M, Li JAL, Uemura N, Wong WK, Burky SA, Hirai H, Chen LP, Griffin JD . 1996 J. Biol. Chem. 271: 25198–25203

  • Schlaepfer DD, Broome MA, Hunter T . 1997 Mol. Cell. Biol. 17: 1702–1713

  • Schraw W, Richmond A . 1995 Biochem. 34: 13760–13767

  • Songyang Z . 2001 Meth. Enzymol. 332: 171–183

  • Songyang Z, Blechner S, Hoagland N, Hoekstra MF, Piwnica-Worms H, Cantley LC . 1994 Curr. Biol. 4: 973–982

  • Songyang Z, Cantley LC . 1998 Methods Mol. Biol. 87: 87–98

  • Sorokin A, Reed E . 1998 Biochem. J. 334: 595–600

  • Spencer KS, Graus-Porta D, Leng J, Hynes NE, Klemke RL . 2000 J. Cell Biol. 148: 385–397

  • Tachibana K, Urano T, Fujita H, Ohashi Y, Kamiguchi K, Iwata S, Hirai H, Morimoto C . 1997 J. Biol. Chem. 272: 29083–29090

  • Takahashi T, Kawahara Y, Taniguchi T, Yokoyama M . 1998 Am. J. Physiol. - Heart Circul. Physiol. 43: H1059–H1065

  • Tamura M, Gu JG, Takino T, Yamada KM . 1999 Cancer Res. 59: 442–449

  • Tanaka S, Morishita T, Hashimoto Y, Hattori S, Nakamura S, Shibuya M, Matuoka K, Takenawa T, Kurata T, Nagashima K, Matsuda M . 1994 Proc. Natl. Acad. Sci. USA 91: 3443–3447

  • Ueki K, Mimura T, Nakamoto T, Sasaki T, Aizawa S, Hirai H, Yano S, Naruse T, Nojima Y . 1998 FEBS Lett. 432: 197–201

  • van Agthoven T, van Agthoven TL, Dekker A, van der Spek PJ, Vreede L, Dorssers LC . 1998 EMBO J. 17: 2799–2808

  • van der Flier S, Brinkman A, Look MP, Kok EM, Meijer-van Gelder ME, Klijn JG, Dorssers LC, Foekens JA . 2000a J. Natl. Cancer Inst. 92: 120–127

  • van der Flier S, Chan CM, Brinkman A, Smid M, Johnston SR, Dorssers LC, Dowsett M . 2000b Int. J. Cancer 89: 465–468

  • Verbeek BS, Vroom TM, Adriaansen-Slot SS, Ottenhoff-Kalff AE, Geertzema JG, Hennipman A, Rijksen G . 1996 J. Pathol. 180: 383–388

  • Vuori K, Hirai H, Aizawa S, Ruoslahti E . 1996 Mol. Cell. Biol. 16: 2606–2613

  • Vuori K, Ruoslahti E . 1995 J. Biol. Chem. 270: 22259–22262

  • Wang X, Weng LP, Yu Q . 2000 Oncogene 19: 2346–2353

  • Weidow CL, Black DS, Bliska JB, Bouton AH . 2000 Cell. Microbiol. 2: 549–560

  • Weng LP, Wang X, Yu Q . 1999 Genes Cells 4: 185–196

  • Wilson LK, Parsons SJ . 1990 Oncogene 5: 1471–1480

  • Xing L, Ge C, Zeltser R, Maskevitch G, Mayer BJ, Alexandropoulos K . 2000 Mol. Cell. Biol. 20: 7363–7377

  • Yamakita Y, Totsukawa G, Yamashiro S, Fry D, Zhang XO, Hanks SK, Matsumura F . 1999 J. Cell Biol. 144: 315–324

  • Yoshizumi M, Abe J, Haendeler J, Huang Q, Berk BC . 2000 J. Biol. Chem. 275: 11706–11712

  • Zachary I, Sinnett-Smith J, Turner CE, Rozengurt E . 1993 J. Biol. Chem. 268: 22060–22065

  • Zhu T, Goh EL, Lobie PE . 1998 J. Biol. Chem. 273: 10682–10689

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Acknowledgements

The authors would like to apologize in advance for any omissions or oversights in this review. We would like to thank past and present members of the lab and colleagues within the Department of Microbiology for their insight and helpful discussions. We would like to gratefully acknowledge support of our work by the National Science Foundation (MCB-9723820 and MCB-0078022) and the Thomas F Jeffress and Kate Miller Jeffress Memorial Trust (J-421 and J556).

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Bouton, A., Riggins, R. & Bruce-Staskal, P. Functions of the adapter protein Cas: signal convergence and the determination of cellular responses. Oncogene 20, 6448–6458 (2001). https://doi.org/10.1038/sj.onc.1204785

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