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Proximal Signals and the Control of S-Phase Entry in Interleukin-2-Stimulated T Lymphocytes

  • Robert T. Abraham
  • Larry M. Karnitz
  • Leigh Ann Burns
  • Gregory J. Brunn
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 365)

Abstract

Stimulation of resting, G0-phase T lymphocytes with antigenic peptides presented in the context of self-MHC triggers a pleiotropic activation program that culminates in cell-cycle entry and the expression of high-affinity receptors for T-cell-derived growth factors. The principal growth and differentiation factor for antigen-activated T lymphocytes is the T-cell-derived cytokine, interleukin-2 (IL-2). Binding of IL-2 to the high-affinity IL-2 receptor (IL-2R) drives the progression of activated, G1-phase T cells into S-phase and, ultimately, mitosis. The intracellular pathways through which IL-2R occupancy provokes this cell-cycle progression response remains an area of intense interest in the field of T-cell biology.

Keywords

Tyrosine Phosphorylation High Molecular Weight Complex Proximal Signal Mitogenic Signal Transduction Tyrosine Phosphorylation Signal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    D. Cosman, S.D. Lyman, R.L. Idzerda, M.P. Beckmann, L.S. Park, R.G. Goodwin, and C.J. March, A new cytokine receptor superfamily, Trends Biochem. Sci. 15:265 (1990).PubMedCrossRefGoogle Scholar
  2. 2.
    D.A. Cantrell and K.A. Smith, The interleukin-2 T-cell system: A new cell growth model, Science 224:1312 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    M.W. Kirschner, The biochemical nature of the cell cycle, in: “Important Advances in Oncology,” V.T. DeVita, Jr., S. Hellman, and S.A. Rosenberg, eds., J.B. Lippincott Co., Philadelphia (1992).Google Scholar
  4. 4.
    C.J. Sherr, Mammalian G1 cyclins, Cell 73:1059 (1993).PubMedCrossRefGoogle Scholar
  5. 5.
    L.C. Cantley, K.R. Auger, C. Carpenter, B. Duckworth, A. Graziani, R. Kapeller, and S. Soltoff, Oncogenes and signal transduction, Cell 64:281 (1991).PubMedCrossRefGoogle Scholar
  6. 6.
    C.P. Downes and A.N. Carter, Phosphoinositide 3-kinase: A new effector in signal transduction? Cell. Signal. 3:501 (1991).PubMedCrossRefGoogle Scholar
  7. 7.
    J.A. Augustine, S.L. Sutor, and R.T. Abraham, Interleukin 2-and polyomavirus middle T antigen-induced modification of phosphatidylinositol 3-kinase activity in activated T lymphocytes, Mol. Cell. Biol. 11:4431 (1991).PubMedGoogle Scholar
  8. 8.
    L. Karnitz, S.L. Sutor, T. Torigoe, J.C. Reed, M.P. Bell, D.J. McKean, P.J. Leibson, and R.T. Abraham, Effects of p56lck deficiency on the growth and cytolytic effector function of an interleukin-2-dependent cytotoxic T-cell line, Mol. Cell. Biol. 12:4521 (1992).PubMedGoogle Scholar
  9. 9.
    H. MacArthur and G. Walter, Monoclonal antibodies specific for the carboxy-terminus of simian virus 40 large T antigen, J. Virol. 52:483 (1984).PubMedGoogle Scholar
  10. 10.
    R. Ren, B.J. Mayer, P. Cicchetti, and D. Baltimore, Identification of a ten-amino acid proline-rich SH3 binding site, Science 259:1157 (1993).PubMedCrossRefGoogle Scholar
  11. 11.
    T. Satoh, M. Nakafuku, A. Miyajima, and Y. Kaziro, Involvement of ras p21 protein in signal-transduction pathways from interleukin 2, interleukin 3, and colony-stimulating factor, but not from interleukin 4, Proc. Natl. Acad. Sci. USA. 88:3314 (1991).PubMedCrossRefGoogle Scholar
  12. 12.
    J. Posada and J.A. Cooper, Molecular signal integration. Interplay between serine, threonine, and tyrosine phosphorylation, Mol. Biol. Cell. 3:583 (1992).PubMedGoogle Scholar
  13. 13.
    C.M. Crews and R.L. Erikson, Extracellular signals and reversible protein phosphorylation: What to mek of it all, Cell 74:215 (1993).PubMedCrossRefGoogle Scholar
  14. 14.
    W.L. Farrar and D.K. Ferris, Two-dimensional analysis of interleukin 2-regulated tyrosine kinase activation mediated by the p70-75 β subunit of the interleukin 2 receptor, J. Biol. Chem. 264:12562 (1989).PubMedGoogle Scholar
  15. 15.
    J.A. Augustine, J.W. Schlager and R.T. Abraham, Differential effects of interleukin-2 and interleukin-4 on protein tyrosine phosphorylation in factor-dependent murine T cells, Biochim. Biophys. Acta 1052:313 (1990).PubMedCrossRefGoogle Scholar
  16. 16.
    E.M. Saltzman, S.M. Luhowskyj, and J.E. Casnellie, The 75,000-dalton interleukin-2 receptor transmits a signal for the activation of a tyrosine protein kinase, J. Biol. Chem. 264:19979 (1989).PubMedGoogle Scholar
  17. 17.
    G. Pelicci, L. Lanfrancone, F. Grignani, J. McGlade, F. Cavallo, G. Forni, I. Nicoletti, F. Grignani, T. Pawson, and P.G. Pelicci, A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction, Cell 70:93 (1992).PubMedCrossRefGoogle Scholar
  18. 18.
    L.A. Burns, L.M. Karnitz, S.L. Sutor, and R.T. Abraham, Interleukin-2-induced tyrosine phosphorylation of p52shc in T lymphocytes, J. Biol. Chem. 268:17659 (1993).PubMedGoogle Scholar
  19. 19.
    S.E. Egan, B.W. Giddings, M.W. Brooks, L. Buday, A.M. Sizeland, and R.A. Weinberg, Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation, Nature 363:45 (1993).PubMedCrossRefGoogle Scholar
  20. 20.
    J. Schlessinger, How receptor tyrosine kinases activate Ras, Trends Biochem. Sci. 18:273 (1993).PubMedCrossRefGoogle Scholar
  21. 21.
    N.H. Sigal and F.J. Dumont, Cyclosporin A, FK-506, and rapamycin: Pharmacologic probes of lymphocytes signal transduction, in: “Annual Review of Immunology,” W.E. Paul, ed., Annual Reviews, Inc., Palo Alto (1992).Google Scholar
  22. 22.
    S.L. Schreiber and G.R. Crabtree, The mechanism of action of cyclosporin A and FK506, Immunol. Today 13:136 (1992).PubMedCrossRefGoogle Scholar
  23. 23.
    F.J. Dumont, M.R. Melino, M.J. Staruch, S.L. Koprak, PA. Fischer, and N.H. Sigal, The immunosuppressive macrolides FK-506 and rapamycin act as reciprocal antagonists in murine T cells, J. Immunol. 144:1418 (1990).PubMedGoogle Scholar
  24. 24.
    A. Koff, M. Ohtsuki, K. Polyak, J.M. Roberts, and J. Massagué, Negative regulation of G1 in mammalian cells: Inhibition of cyclin E-dependent kinase by TGF-β, Science 260:536 (1993).PubMedCrossRefGoogle Scholar
  25. 25.
    A. Koff, A. Giordano, D. Desai, K. Yamashita, J.W. Harper, S. Elledge, T. Nishimoto, D.O. Morgan, B.R. Franza, and J.M. Roberts, Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle, Science 257:1689 (1992).PubMedCrossRefGoogle Scholar
  26. 26.
    W.G. Morice, G. Wiederrecht, G.J. Brunn, J.J. Siekierka, and R.T. Abraham, Rapamycin inhibition of interleukin-2-dependent p33cdk2 and p34cdc2 kinase activation in T lymphocytes, J. Biol. Chem. 268:22737 (1993).PubMedGoogle Scholar
  27. 27.
    T. Kono, Y. Minami, and T. Taniguchi, The interleukin-2 receptor complex and signal transduction: role of the β-chain, Sem. Immunol. 5:299 (1993).CrossRefGoogle Scholar
  28. 28.
    T. Hunter, Braking the cycle, Cell 75:839 (1993).PubMedCrossRefGoogle Scholar
  29. 29.
    J. Chung, C.J. Kuo, G.R. Crabtree, and J. Blenis, Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases, Cell 69:1227 (1992).PubMedCrossRefGoogle Scholar
  30. 30.
    V. Calvo, CM. Crews, TA. Vik, and B.E. Bierer, Interleukin 2 stimulation of p70 S6 kinase activity is inhibited by the immunosuppressant rapamycin, Proc. Natl. Acad. Sci. USA 89:7571 (1992).PubMedCrossRefGoogle Scholar
  31. 31.
    C.J. Kuo, J. Chung, D.F. Fiorentino, W.M. Flanagan, J. Blenis, and G.R. Crabtree, Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase, Nature 358:70 (1992).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Robert T. Abraham
    • 1
  • Larry M. Karnitz
    • 1
  • Leigh Ann Burns
    • 1
  • Gregory J. Brunn
    • 1
  1. 1.Departments of ImmunologyPharmacology Mayo Clinic/FoundationRochesterUSA

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