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  • Review Article
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Transgenic analysis of thymocyte signal transduction

Nature Reviews Immunology volume 2, pages 20–27 (2002)Cite this article

Key Points

  • As T cells develop within the thymus, they pass through an ordered sequence of differentiation and proliferation checkpoints to result in the production of mature, correctly selected, non-autoreactive, peripheral T cells.

  • Transgenic studies in mice have been fundamental for the genetic dissection of the signal-transduction pathways that occur during T-cell development.

  • T-cell-specific promoters, including the human CD2 promoter and the mouse proximal p56lck promoter, have been used to drive T-lineage expression of dominant-negative or gain-of-function mutants of signalling proteins. The heterogeneity and timing of transgene expression can affect the phenotype of transgenic mice and needs to be carefully considered.

  • The specificity and mode of action of any putative dominant-negative mutants needs to be investigated prior to the generation of transgenic mice, so various problems in the interpretation of data can be avoided. Similarly, with constitutively active mutants, the localization of the mutant protein must be considered.

  • These transgenic approaches need to be used with full awareness of their limitations. The development of new transgenic vectors, which allow for the inducible expression of transgenes, and more detailed biochemical knowledge of signal-transduction pathways will enable further transgenic studies to be performen to increase our understanding of the processes that control thymoctye development.

Abstract

This review examines the value of transgenic studies in mice for the genetic dissection of signal-transduction pathways relevant to thymus development. T-cell development in the thymus is controlled by an ordered sequence of differentiation and proliferation checkpoints that culminate in the production of correctly selected, non-autoreactive, peripheral T lymphocytes. Work in transgenic mice has been fundamental for the preparation of genetic maps of signal-transduction pathways that control T-cell development. This review discusses how tyrosine kinases, guanine-nucleotide-binding proteins and transcription factors converge to control T-cell differentiation and proliferation in the immune system.

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Figure 1: Summary of the main stages of thymocyte development.
Figure 2: Schematic of pre-TCR signalling.

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References

  1. Crompton, T., Gilmour, K. C. & Owen, M. J. The MAP kinase pathway controls differentiation from double-negative to double-positive thymocyte. Cell 86, 243–251 (1996).

    CAS  PubMed  Google Scholar 

  2. Pallard, C. et al. Distinct roles of the phosphatidylinositol 3-kinase and STAT5 pathways in IL-7-mediated development of human thymocyte precursors. Immunity 10, 525–535 (1999).

    CAS  PubMed  Google Scholar 

  3. Perlmutter, R. M. & Alberola-Ila, J. The use of dominant-negative mutations to elucidate signal transduction pathways in lymphocytes. Curr. Opin. Immunol. 8, 285–290 (1996).

    CAS  PubMed  Google Scholar 

  4. Rincon, M. MAP-kinase signaling pathways in T cells. Curr. Opin. Immunol. 13, 339–345 (2001).Two excellent reviews: reference 3 covers most of the key experiments using transgenesis to look at the function of SRC kinases and Ras GTPases in the thymus; reference 4 is a comprehensive analysis of how MAP kinases control lymphocyte biology.

    CAS  PubMed  Google Scholar 

  5. Allen, J. M., Forbush, K. A. & Perlmutter, R. M. Functional dissection of the Lck proximal promoter. Mol. Cell. Biol. 12, 2758–2768 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhumabekov, T., Corbella, P., Tolaini, M. & Kioussis, D. Improved version of a human CD2 minigene based vector for T cell-specific expression in transgenic mice. J. Immunol. Methods 185, 133–140 (1995).

    CAS  PubMed  Google Scholar 

  7. Ellmeier, W., Sawada, S. & Littman, D. R. The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu. Rev. Immunol. 17, 523–554 (1999).

    CAS  PubMed  Google Scholar 

  8. Cleverley, S., Henning, S. & Cantrell, D. Inhibition of Rho at different stages of thymocyte development gives different perspectives on Rho function. Curr. Biol. 9, 657–660 (1999).

    CAS  PubMed  Google Scholar 

  9. Buckland, J., Pennington, D. J., Bruno, L. & Owen M. J. Co-ordination of the expression of the protein tyrosine kinase p56lck with the pre-T cell receptor during thymocyte development. Eur. J. Immunol. 30, 8–18 (2000).

    CAS  PubMed  Google Scholar 

  10. Gomez, M., Tybulewicz, V. & Cantrell, D. A. Control of pre-T cell proliferation and differentiation by the GTPase Rac-1. Nature Immunol. 1, 348–352 (2000).

    CAS  Google Scholar 

  11. van Weeren, P. C., de Bruyn, K. M., de Vries-Smits, A. M., van Lint, J. & Burgering, B. M. Essential role for protein kinase B (PKB) in insulin-induced glycogen synthase kinase 3 inactivation. Characterization of dominant-negative mutant of PKB. J. Biol. Chem. 273, 13150–13156 (1998).

    CAS  PubMed  Google Scholar 

  12. Garcia-Paramio, P., Cabrerizo, Y., Bornancin, F. & Parker, P. J. The broad specificity of dominant inhibitory protein kinase C mutants infers a common step in phosphorylation. Biochem. J. 333, 631–636 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kuo, C. T. & Leiden, J. M. Transcriptional regulation of T lymphocyte development and function. Annu. Rev. Immunol. 17, 149–187 (1999).

    CAS  PubMed  Google Scholar 

  14. Voll, R. E. et al. NF-κB activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development. Immunity 13, 677–689 (2000).

    CAS  PubMed  Google Scholar 

  15. Hettmann, T. & Leiden, J. M. NF-κB is required for the positive selection of CD8+ thymocytes. J. Immunol. 165, 5004–5010 (2000).

    CAS  PubMed  Google Scholar 

  16. Pearson, R. & Weston, K. c-Myb regulates the proliferation of immature thymocytes following β-selection. EMBO J. 19, 6112–6120 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Taylor, D., Badiani, P. & Weston, K. A dominant interfering Myb mutant causes apoptosis in T cells. Genes Dev. 10, 2732–2744 (1996).

    CAS  PubMed  Google Scholar 

  18. Newton, K., Harris, A. W., Bath, M. L., Smith, K. G. & Strasser, A. A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J. 17, 706–718 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Newton, K., Harris, A. W. & Strasser, A. FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor. EMBO J. 19, 931–941 (2000).References 18 and 19 show that the adaptor FADD/MORT1 induces pro-apoptopic cell-death responses but, in parallel, can control T-cell proliferation.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Newton, K., Kurts, C., Harris, A. W. & Strasser, A. Effects of a dominant interfering mutant of FADD on signal transduction in activated T cells. Curr. Biol. 11, 273–276 (2001).

    CAS  PubMed  Google Scholar 

  21. Genot, E., Cleverley, S., Henning, S. & Cantrell, D. Multiple p21ras effector pathways regulate nuclear factor of activated T cells. EMBO J. 15, 3923–3933 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Genot, E. & Cantrell, D. A. Ras regulation and function in lymphocytes. Curr. Opin. Immunol. 12, 289–294 (2000).

    CAS  PubMed  Google Scholar 

  23. Acuto, O. & Cantrell, D. T cell activation and the cytoskeleton. Annu. Rev. Immunol. 18, 165–184 (2000).

    CAS  PubMed  Google Scholar 

  24. Cantrell, D. Phosphoinositide 3-kinase signalling pathways. J. Cell Sci. 114, 1439–1445 (2001).

    CAS  PubMed  Google Scholar 

  25. Cantrell D. Protein kinase B (Akt) regulation and function in T lymphocytes. Semin. Immunol. (in the press)

  26. Ahmed, N. N. et al. The proteins encoded by c-akt and v-akt differ in post-translational modification, subcellular localization and oncogenic potential. Oncogene 8, 1957–1963 (1993).

    CAS  PubMed  Google Scholar 

  27. Dufner, A., Andjelkovic, M., Burgering, B. M., Hemmings, B. A. & Thomas, G. Protein kinase B localization and activation differentially affect S6 kinase 1 activity and eukaryotic translation initiation factor4E-binding protein 1 phosphorylation. Mol. Cell. Biol. 19, 4525–4534 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Jones, R. G. et al. Protein kinase B regulates T lymphocyte survival, nuclear factor κB activation, and Bcl-XL levels in vivo. J. Exp. Med. 191, 1721–1734 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Parsons, M. J. et al. Expression of active protein kinase B in T cells perturbs both T and B cell homeostasis and promotes inflammation. J. Immunol. 167, 42–48 (2001).

    CAS  PubMed  Google Scholar 

  30. Astoul, E., Watton, S. & Cantrell, D. A. The dynamics of protein kinase B regulation during B cell antigen receptor engagement. J. Cell Biol. 145, 1511–1520 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Mombaerts, P., Anderson, S. J., Perlmutter, R. M., Mak, T. W. & Tonegawa, S. An activated lck transgene promotes thymocyte development in RAG-1 mutant mice. Immunity 1, 261–267 (1994).

    CAS  PubMed  Google Scholar 

  32. Iritani, B. M., Alberola-Ila, J., Forbush, K. A. & Perimutter, R. M. Distinct signals mediate maturation and allelic exclusion in lymphocyte progenitors. Immunity 10, 713–722 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Swat, W., Shinakai, Y., Cheng, H. -L., Davidson, L. & Alt, F. W. Activated Ras signals differentiation and expansion of CD4+8+ thymocytes. Proc. Natl Acad. Sci. USA 93, 4683–4687 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Anderson, S. J., Levin, S. D. & Perlmutter, R. M. Protein tyrosine kinase p56lck controls allelic exclusion of T-cell receptor β-chain genes. Nature 365, 552–554 (1993).

    CAS  PubMed  Google Scholar 

  35. Henning, S. W. & Cantrell, D. A. p56lck signals for regulating thymocyte development can be distinguished by their dependency on Rho-function. J. Exp. Med. 188, 931–939 (1998).This reference, and reference 32 , show that the signals that control pre-T-cell proliferation, differentiation and the processes of allelic exclusion are distinct.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Costello, P. S., Cleverley, S. C., Galandrini, R., Henning, S. W. & Cantrell, D. A. The GTPase rho controls a p53-dependent survival checkpoint during thymopoiesis. J. Exp. Med. 192, 77–85 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Corre, I., Gomez, M., Vielkind, S. & Cantrell, D. The GTPase RhoA regulates preTCR and αβTCR mediated responses. J. Exp. Med. (in the press).

  38. Lamarche, N. et al. Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK/SAPK MAP kinase cascade. Cell 87, 519–529 (1996). | PubMed |

    CAS  PubMed  Google Scholar 

  39. Bishop A. L. & Hall A. Rho GTPases and their effector proteins. Biochem. J. 348, 241–255 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Fischer, K. D. et al. Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes. Nature 374, 474–477 (1995).

    CAS  PubMed  Google Scholar 

  41. Fischer, K. D. et al. Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor. Curr. Biol. 8, 554–562 (1998).

    CAS  PubMed  Google Scholar 

  42. Turner, M. et al. A requirement for the Rho-family GTP exchange factor Vav in positive and negative selection of thymocytes. Immunity 7, 451–460 (1997).

    CAS  PubMed  Google Scholar 

  43. Strasser, A., Harris, A. W. & Cory, S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67, 889–899 (1991).

    CAS  PubMed  Google Scholar 

  44. Strasser, A., Harris, A. W., Jacks, T. & Cory, S. DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by Bcl-2. Cell 79, 329–339 (1994).

    CAS  PubMed  Google Scholar 

  45. Strasser, A., Harris, A. W., Huang, D. C. S., Krammer, H. & Cory, S. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J. 14, 6136–6147 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. O'Reilly, L. A., Harris, A. W. & Strasser, A. bcl-2 transgene expression promotes survival and reduces proliferation of CD3−CD4−CD8− T cell progenitors. Int. Immunol. 9, 1291–1301 (1997).

    CAS  PubMed  Google Scholar 

  47. von Freeden-Jeffry, U., Solvason, N., Howard, M. & Murray, R. The earliest T lineage-commited cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. Immunity 7, 147–154 (1997).

    CAS  PubMed  Google Scholar 

  48. Maraskovsky, E. et al. Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant Rag-1−/− mice. Cell 89, 1011–1019 (1997).

    CAS  PubMed  Google Scholar 

  49. Akashi, K., Kondo, M., von Freeden-Jeffry, U., Murray, R. & Weissman I. L. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell 89, 1033–1041 (1997).References 46–48 show that developmental defects associated with loss of IL-7 signals in the thymus can be partially rescued by ectopic expression of Bcl-2; therefore, indicating that a principal function for IL-7 in T-cell development is the control of cell survival.

    CAS  PubMed  Google Scholar 

  50. Gallandrini, R., Henning, S. & Cantrell, D. A. Different functions for the GTPase Rho in prothymocytes and late pre-T cells. Immunity 7, 163–174 (1997).

    Google Scholar 

  51. von Boehmer, H. et al. Pleiotropic changes controlled by the pre-T-cell receptor. Curr. Opin. Immunol. 11, 135–142 (1999).

    CAS  PubMed  Google Scholar 

  52. Irving, B. A., Alt, F. W. & Killeen, N. Thymocyte development in the absence of pre-T cell receptor extracellular immunoglobulin domains. Science 280, 905–908 (1998).

    CAS  PubMed  Google Scholar 

  53. Wiest, D. L., Berger, M. A. & Carleton, M. Control of early thymocyte development by the pre-T cell receptor complex: a receptor without a ligand? Semin. Immunol. 11, 251–262 (1999).

    CAS  PubMed  Google Scholar 

  54. Fehling, H. J. et al. Restoration of thymopoiesis in pTα−/− mice by anti-CD3α antibody treatment or with transgenes encoding activated Lck or tailless pTα. Immunity 6, 703–714 (1997).

    CAS  PubMed  Google Scholar 

  55. O'Shea, C. C., Thornell, A. P., Rosewell, I. R., Hayes B. & Owen, M. J. Exit of the pre-TCR from the ER/cis-Golgi is necessary for signaling differentiation, proliferation, and allelic exclusion in immature thymocytes. Immunity 7, 591–599 (1997).

    CAS  PubMed  Google Scholar 

  56. Saint-Ruf, C. et al. Different initiation of pre-TCR and γδ TCR signalling. Nature 406, 524–527 (2000).

    CAS  PubMed  Google Scholar 

  57. Gibbons, D. et al. The biological activity of natural and mutant pTα alleles. J. Exp. Med. 194, 695–704 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Gossen, M. et al. Transcriptional activation by tetracyclines in mammalian cells. Science 268, 1766–1769 (1995).

    CAS  PubMed  Google Scholar 

  59. Witherden, D. et al. Tetracycline-controllable selection of CD4+ T cells: half-life and survival signals in the absence of major histocompatibility complex class II molecules. J. Exp. Med. 191, 355–364 (2000).

    CAS  PubMed  Google Scholar 

  60. Legname, G. et al. Inducible expression of a p56lck transgene reveals a central role for Lck in the differentiation of CD4 SP thymocytes. Immunity 12, 537–546 (2000).

    CAS  PubMed  Google Scholar 

  61. Seddon, B., Legname, G., Tomlinson, P. & Zamoyska, R. Long-term survival but impaired homeostatic proliferation of naive T cells in the absence of p56lck. Science 290, 127–131 (2000).Pioneering studies that set the standard for how to use tetracycline-controlled expression vectors to probe the role of signalling molecules in T-cell development and peripheral T-cell proliferation and survival.

    CAS  PubMed  Google Scholar 

  62. Littlewood, T. D., Hancock, D. C., Danielian, P. S., Parker, M. G. & Evan, G. I. A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Res. 23, 1686–1690 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Pelengaris, S., Littlewood, T., Khan, M., Elia, G. & Evan, G. Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol. Cell 3, 565–577 (1999).

    CAS  PubMed  Google Scholar 

  64. Kohn, A. D. et al. Construction of a conditionally active version of the serine/threonine kinase Akt. J. Biol. Chem. 273, 11937–11943 (1998).

    CAS  PubMed  Google Scholar 

  65. Mak, T. W., Penninger, J. M. & Ohashi, P. S. Knockout mice: a paradigm shift in modern immunology. Nature Rev. Immunol. 1, 11–19 (2001).

    CAS  Google Scholar 

  66. Le, Y. & Sauer, B. Conditional gene knockout using Cre recombinase. Mol. Biotechnol. 17, 269–275 (2001).

    CAS  PubMed  Google Scholar 

  67. Metzger, D. & Chambon, P. Site- and time-specific gene targeting in the mouse. Methods 24, 71–80 (2001).

    CAS  PubMed  Google Scholar 

  68. Chaffin, K. E. et al. Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase. EMBO J. 9, 3821–3829 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Chaffin, K. E. & Perlmutter, R. M. A pertussis toxin-sensitive process controls thymocyte emigration. Eur. J. Immunol. 21, 2565–2573 (1991).

    CAS  PubMed  Google Scholar 

  70. Henning, S., Galandrini, R., Hall, A. & Cantrell, D. A. The GTPase Rho has a critical regulatory role in thymocyte development. EMBO. J. 16, 2397–2407 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Swan K. A. et al. Involvement of p21ras distinguishes positive and negative selection in thymocytes. EMBO J. 14, 276–285 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Hogquist, K. RasGRP: the missing link for Ras activation in thymocytes. Trends Immunol. 22, 69 (2001).

    CAS  PubMed  Google Scholar 

  73. Zwartkruis, F. J. & Bos, J. L. Ras and Rap1: two highly related small GTPases with distinct function. Exp. Cell Res. 253, 157–165 (1999).

    CAS  PubMed  Google Scholar 

  74. O'Shea, C. C., Crompton, T., Rosewell, I. R., Hayday, A. C. & Owen, M. J. Raf regulates positive selection. Eur. J. Immunol. 26, 2350–2355 (1996).

    CAS  PubMed  Google Scholar 

  75. Turner, H. et al. Rac-1 regulates nuclear factor of activated T cells (NFAT) C1 nuclear translocation in response to Fcɛ receptor type 1 stimulation of mast cells. J. Exp. Med. 188, 527–537 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Alberola-Ila, J., Forbush, K. A., Seger, R., Krebs, E. G. & Perlmutter, R. M. Selective requirement for MAP kinase activation in thymocyte differentiation. Nature 373, 620–623 (1995).

    CAS  PubMed  Google Scholar 

  77. Alberola-Ila, J., Hogquist, K. A., Swan, K. A., Bevan, M. J. & Perlmutter R. M. Positive and negative selection invoke distinct signaling pathways. J. Exp. Med. 184, 9–18 (1996).

    CAS  PubMed  Google Scholar 

  78. Pages, G. et al. Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice. Science 286, 1374–1377 (1999).The MAP kinases Erk1 and Erk2 are generally thought to have redundant functions; however, this paper shows that loss of Erk1 cannot be compensated for by Erk2 during T-cell maturation.

    CAS  PubMed  Google Scholar 

  79. Seavitt, J. R. et al. Expression of the p56Lck Y505F mutation in CD45-deficient mice rescues thymocyte development. Mol. Cell. Biol. 19, 4200–4208 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Sohn, S. J., Forbush, K. A., Pan, X. C. & Perlmutter, R. M. Activated p56lck directs maturation of both CD4 and CD8 single-positive thymocytes. J. Immunol. 166, 2209–2217 (2001).

    CAS  PubMed  Google Scholar 

  81. Genot, E. M., Parker, P. J. & Cantrell, D. A. Analysis of the role of protein kinase C-α, -ɛ, and -ζ in T cell activation. J. Biol. Chem. 270, 9833–9839 (1995).

    CAS  PubMed  Google Scholar 

  82. Parekh, D. B., Ziegler, W. & Parker, P. J. Multiple pathways control protein kinase C phosphorylation. EMBO J. 19, 496–503 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Matthews, S. A., Rozengurt, E. & Cantrell, D. Protein kinase D. A selective target for antigen receptors and a downstream target for protein kinase C in lymphocytes. J. Exp. Med. 191, 2075–2082 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Matthews, S. A., Rozengurt, E. & Cantrell, D. Characterization of serine 916 as an in vivo autophosphorylation site for protein kinase D/Protein kinase Cμ. J. Biol. Chem. 274, 26543–26549 (1999).

    CAS  PubMed  Google Scholar 

  85. Waldron, R. T. et al. Activation loop Ser744 and Ser748 in protein kinase D are transphosphorylated in vivo. J. Biol. Chem. 276, 32606–32615 (2001).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, WC2A 3PX, UK

    Doreen A. Cantrell

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DATABASES

Flybase

Engrailed

LocusLink

Bcl-2

CD2

CD4

CD8

CD25

CD44

Cdc42

c-Myb

c-Myc

FADD

IL-7

IL-7 receptor

p56lck

PKB

protein kinase C

Rac-1

Raf-1

Rag1

RhoA

Vav1

FURTHER INFORMATION

Doreen Cantrell's lab 

Encylopedia of Life Sciences 

signal transduction: overview

Glossary

GTPases

Signalling proteins that bind guanine nucleotides. They are active in the GTP-bound state and are inactivated when they hydrolyse GTP into GDP.

PRE-T CELLS

A population of cells found in the thymus that undergo rearrangements of the αβ-subunits of the T-cell antigen receptor complex prior to commitment to the T-cell lineage.

GTPase-ACTIVATING PROTEIN

(GAP). A protein that stimulates the intrinsic GTPase activity of small GTPases; for example, for RAS, two GAPs are known, p120 GAP and neurofibromin.

GUANINE NUCLEOTIDE-EXCHANGE FACTOR

(GEF). A protein that catalyses guanine nucleotide exchange on GTPases.

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Cantrell, D. Transgenic analysis of thymocyte signal transduction. Nat Rev Immunol 2, 20–27 (2002). https://doi.org/10.1038/nri703

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