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Regulation of integrin function by T cell activation

Points of Convergence and Divergence

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Abstract

Lymphocyte adhesiveness is dynamically regulated in response to conditions in the extracellular environment. One mechanism of regulation of integrin adhesion receptors involves a rapid, but transient, increase in integrin function upon T lymphocyte activation. These integrin activating signals can be initiated either via ligation of Ig superfamily members that are coupled to tyrosine kinase cascades, such as the CD3/T cell receptor, CD2, and CD28, or by G proteincoupled receptors for chemokines. Analysis of integrin activation induced by CD3/TCR, CD2 and CD28 suggests a critical role for phosphoinositide 3-OH kinase (PI 3-K). This review summarizes recent insights into PI 3-K-dependent regulation of integrin function in leukocytes, including the mechanisms by which these receptors are coupled to PI 3-K, and potential downstream effectors of PI 3-K that regulate integrin-mediated adhesion in leukocytes.

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References

  1. Shimizu Y, Rose DM, Ginsberg MH: Integrins and the immune response. Adv Immunol1999;72: 325–380.

    Article  PubMed  CAS  Google Scholar 

  2. Schwartz MA, Schaller MD, Ginsberg MH: Integrins: emerging paradigms of signal transduction. Annu Rev Cell Biol 1995;11:549–599.

    Article  CAS  Google Scholar 

  3. Springer TA: Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994;76:301–314.

    Article  PubMed  CAS  Google Scholar 

  4. Shattil SJ, Kashiwagi H, Pampori N: Integrin signaling: the platelet paradigm. Blood 1998;91:2645–2657.

    PubMed  CAS  Google Scholar 

  5. Shimizu Y, van Seventer GA, Horgan KJ, Shaw S: Regulated expression and binding of three VLA (β1) integrin receptors on T cells. Nature 1990;345:250–253.

    Article  PubMed  CAS  Google Scholar 

  6. Dustin ML, Springer TA: T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 1989;341:619–624.

    Article  PubMed  CAS  Google Scholar 

  7. Shimizu Y, van Seventer GA, Ennis E, Newman W, Horgan KJ, Shaw S: Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion. J Exp Med 1992;175:577–582.

    Article  PubMed  CAS  Google Scholar 

  8. van Kooyk Y, van de Wiel-van Kemenade P, Weder P, Kuijpers TW, Figdor CG: Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes. Nature 1989;342: 811–813.

    Article  PubMed  Google Scholar 

  9. Tanaka Y, Adams DH, Hubscher S, Hirano H, Siebenlist U, Shaw S: T-cell adhesion induced by proteoglycan-immobilized cytokine MIP1β. Nature 1993;361:79–82.

    Article  PubMed  CAS  Google Scholar 

  10. Carr MW, Alon R, Springer TA: The C-C chemokine MCP-1 differentially modulates the avidity of β1 and β2 integrins on T lymphocytes. Immunity 1996;4:179–187.

    Article  PubMed  CAS  Google Scholar 

  11. Lloyd AR, Oppenheim JJ, Kelvin DJ, Taub DD: Chemokines regulate T cell adherence to recombinant adhesion molecules and extracellular matrix proteins. J Immunol 1996:156:932–938.

    PubMed  CAS  Google Scholar 

  12. Gunn MD, Tangemann K, Tam C, Cyster JG, Rosen SD, Williams LT: A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. Proc Natl Acad Sci USA 1998;95:258–263.

    Article  PubMed  CAS  Google Scholar 

  13. Campbell JJ, Hedrick J, Zlotnik A, Siani MA, Thompson DA, Butcher EC: Chemokines and the arrest of lymphocytes rolling under flow conditions. Science 1998;279:381–384.

    Article  PubMed  CAS  Google Scholar 

  14. Ward SG, Bacon K, Westwick J: Chemokines and T lymphocytes: More than an attraction. Immunity 1998;9:1–11.

    Article  PubMed  CAS  Google Scholar 

  15. Tanaka Y, Albelda SM, Horgan KJ, van Seventer GA, Shimizu Y, Newman W, Hallam J, Newman PJ, Buck CA, Shaw S: CD31 expressed on distinctive T cell subsets is a preferential amplifier of β 1 integrin-mediated adhesion. J Exp Med 1992;176:245–253.

    Article  PubMed  CAS  Google Scholar 

  16. Stewart MP, McDowall A, Hogg N: LFA-1-mediated adhesion is regulated by cytoskeletal restraint and by a Ca2+-dependent protease, calpain. J Cell Biol 1998;140:699–707.

    Article  PubMed  CAS  Google Scholar 

  17. Bazzoni G, Hemler ME: Are changes in integrin affinity and conformation overemphasized. Trends Biochem Sci 1998;23:30–34.

    Article  PubMed  CAS  Google Scholar 

  18. Stewart MP, Cabanas C, Hogg N: T cell adhesion to intercellular adhesion molecule-1 (ICAM-1) is controlled by cell spreading and the activation of integrin LFA-1. J Immunol 1996;156:1810–1817.

    PubMed  CAS  Google Scholar 

  19. Faull RJ, Kovach NL, Harlan JM, Ginsberg MH: Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences. J Exp Med 1994;179:1307–1316.

    Article  PubMed  CAS  Google Scholar 

  20. Kucik DF, Dustin ML, Miller JM, Brown EJ: Adhesion-activating phorbol ester increases the mobility of leukocyte integrin LFA-1 in cultured lymphocytes. J Clin Invest 1996;97:2139–2144.

    PubMed  CAS  Google Scholar 

  21. Linsley PS, Ledbetter JA: Therole of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol 1993;11:191–212.

    PubMed  CAS  Google Scholar 

  22. June CH, Bluestone JA, Nadler LM, Thompson CB: The B7 and CD28 receptor families. Immunol Today 1994;15:321–331.

    Article  PubMed  CAS  Google Scholar 

  23. Bluestone JA: New perspectives of CD28-B7-mediated T cell costimulation. Immunity 1995;2:555–559.

    Article  PubMed  CAS  Google Scholar 

  24. Thompson CB: Distinct roles for the costimulatory ligands B7-1 and B72 in T helper cell differentiation. Cell 1995;81:979–982.

    Article  PubMed  CAS  Google Scholar 

  25. Turcovski-Corrales SM, Fenton RG, Peltz G, Taub DD: CD28:B7 interactions promote T cell adhesion. Eur J Immunol 1995;25:3087–3093.

    Article  PubMed  CAS  Google Scholar 

  26. August A, Gibson S, Kawakami Y, Kawakami T, Mills GB, Dupont B: CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line. Proc Natl Acad Sci USA 1994;91:9347–9351.

    Article  PubMed  CAS  Google Scholar 

  27. Lu YL, Cuevas B, Gibson S, Khan H, Lapushin R, Imboden J, Mills GB: Phosphatidylinositol 3-kinase is required for CD28 but not CD3 regulation of the TEC family tyrosine kinase EMT/ITK/TSK: Functional and physical interaction of EMT with phosphatidylinositol 3-kinase. J Immunol 1998;161:5404–5412.

    PubMed  CAS  Google Scholar 

  28. Lu Y, Granelli-Piperno A, Bjorndahl JM, Phillips CA, Trevillyan JM: CD28-induced T cell activation: Evidence for a proteintyrosine kinase signal transduction pathway. J Immunol 1992; 149:24–29.

    PubMed  CAS  Google Scholar 

  29. Fraser JD, Newton ME, Weiss A: CD28 and T cell antigen receptor signal transduction coordinately regulate interleukin 2 gene expression in response to superantigen stimulation. J Exp Med 1992;175: 1131–1134.

    Article  PubMed  CAS  Google Scholar 

  30. Raab M, Cai YC, Bunnell SC, Heyeck SD, Berg LJ, Rudd CE: p56Lck and p59Fyn regulate CD28 binding to phosphatidylinositol 3-kinase, growth factor receptorbound protein GRB-2, and T cell-specific protein-tyrosine kinase ITK: implications for T-cell costimulation. Proc Natl Acad Sci USA 1995;92:8891–8895.

    Article  PubMed  CAS  Google Scholar 

  31. Prasad KVS, Cai Y-C, Raab M, Duckworth B, Cantley L, Shoelson SE, Rudd CE: T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-XaaMet motif. Proc Natl Acad Sci USA 1994;91:2834–2838.

    Article  PubMed  CAS  Google Scholar 

  32. August A, Dupont B: CD28 of T lymphocytes associates with phosphatidylinositol 3-kinase. Int Immunol 1994;6:769–774.

    Article  PubMed  CAS  Google Scholar 

  33. Ward SG: CD28: a signalling perspective. Biochem J 1996;318: 361–377.

    PubMed  CAS  Google Scholar 

  34. Rudd CE: Upstream-downstream: CD28 cosignaling pathways and T cell function. Immunity 1996;4: 527–534.

    Article  PubMed  CAS  Google Scholar 

  35. Hutchcroft JE, Bierer BE: Signaling through CD28/CTLA-4 family receptors puzzling participation of phosphatidylinositol-3 kinase. J Immunol 1996;156:4071–4074.

    PubMed  CAS  Google Scholar 

  36. Fruman DA, Meyers RE, Cantley LC: Phosphoinositide kinases. Annu Rev Biochem 1998;67:481–507.

    Article  PubMed  CAS  Google Scholar 

  37. Lemmon MA, Ferguson KM: Pleckstrin homology domains. Curr Top Microbiol Immunol 1998;228:39–74.

    PubMed  CAS  Google Scholar 

  38. Marte BM, Downward J: PKB/ Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem Sci 1997;22:355–358.

    Article  PubMed  CAS  Google Scholar 

  39. Klippel A, Kavanaugh WM, Pot D, Williams LT: A specific product of phosphatidylinositol 3-kinase directly activates the protein kinase Akt through its pleckstrin homology domain. Mol Cell Biol 1997;17:338–344.

    PubMed  CAS  Google Scholar 

  40. Lemmon MA, Falasca M, Ferguson KM, Schlessinger J: Regulatory recruitment of signalling molecules to the cell membrane by pleckstrin-homology domains. Trends Cell Biol 1997; 7:237–242.

    Article  CAS  Google Scholar 

  41. Falasca M, Logan SK, Lehto VP, Baccante G, Lemmon MA, Schlessinger J: Activation of phospholipase Cγby PI 3-kinaseinduced PH domain-mediated membrane targeting. EMBO J 1998;17:414–422.

    Article  PubMed  CAS  Google Scholar 

  42. Nagel W, Zeitlmann L, Schilcher P, Geiger C, Kolanus J, Kolanus W: Phosphoinositide 3-OH kinase activates the β2 integrin adhesion pathway and induces membrane recruitment of cytohesin-1. J Biol Chem 1998; 273:14,853–14,861.

    Article  CAS  Google Scholar 

  43. Zell T, Hunt SW, III, Finkelstein LD, Shimizu Y: CD28-mediated upregulation of β1 integrin-mediated adhesion involves phosphatidylinositol 3-kinase. J Immunol 1996; 156:883–886.

    PubMed  CAS  Google Scholar 

  44. Zell T, Warden CS, Chan ASH, Cook ME, Dell CL, Hunt SW, III, Shimizu Y: Regulation of β1integrin-mediated adhesion by the Cbl adapter protein. Curr Biol 1998;8:814–822.

    Article  PubMed  CAS  Google Scholar 

  45. Schneider H, Prasad KVS, Shoelson SE, Rudd CE: CTLA4 binding to the lipid kinase phosphatidylinositol 3-kinase in T cells. J Exp Med 1995;181:351–355.

    Article  PubMed  CAS  Google Scholar 

  46. Chan ASH, Mobley JL, Fields GB, Shimizu Y: CD7-mediated regulation of integrin adhesiveness on human T cells involves tyrosine phosphorylation-dependent activation of phosphatidylinositol 3-kinase. J Immunol 1997;159:934–942.

    PubMed  CAS  Google Scholar 

  47. Mobley JL, Ennis E, Shimizu Y: Differential activation-dependent regulation of integrin function in cultured human T-leukemic cell lines. Blood 1994;83:1039–1050.

    PubMed  CAS  Google Scholar 

  48. Liu YC, Altman A: Cbl: complex formation and functional implications. Cell Signal 1998;10:377–385.

    Article  PubMed  CAS  Google Scholar 

  49. Lupher ML, Jr., Andoniou CE, Bonita D, Miyake S, Band H: The c-Cbl oncoprotein. Int J Biochem Cell Biol 1998;30:439–444.

    Article  PubMed  CAS  Google Scholar 

  50. Thien CB, Langdon WY:c-Cbl:a regulator of T cell receptor-mediated signalling. Immunol Cell Biol 1998;76:473–482.

    Article  PubMed  CAS  Google Scholar 

  51. Andoniou CE, Thien CBF, Langdon WY: Tumour induction by activated abl involves tyrosine phosphorylation of the product of the cbl oncogene. EMBO J 1994;13:4515–4523.

    PubMed  CAS  Google Scholar 

  52. Thien CBF, Langdon WY: Tyrosine kinase activity of the EGF receptor is enhanced by the expression of oncogenic 70Z-Cbl. Oncogene 1997;15:2909–2919.

    Article  PubMed  CAS  Google Scholar 

  53. Meuer SC, Hussey RE, Fabbi M, Fox D, Acuto O, Fitzgerald KA, Hodgdon JC, Protentis JP, Schlossman SF, Reinherz EL: An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell 1984;36:897–906.

    Article  PubMed  CAS  Google Scholar 

  54. Gollob JA, Li J, Reinherz EL, Ritz J: CD2 regulates responsiveness of activated T cells to interleukin 12. J Exp Med 1995;182:721–731.

    Article  PubMed  CAS  Google Scholar 

  55. Bell GM, Imboden JB: CD2 and the regulation of T cell anergy. J Immunol 1995; 155:2805–2807.

    PubMed  CAS  Google Scholar 

  56. Boussiotis VA, Freeman GJ, Griffin JD, Gray GS, Gribben JG, Nadler LM: CD2 is involved in maintenance and reversal of human alloantigenspecific clonal anergy. J Exp Med 1994;180:1665–1673.

    Article  PubMed  CAS  Google Scholar 

  57. Shimizu Y, Mobley JL, Finkelstein LD, Chan ASH: A role for phosphatidylinositol 3-kinase in the regulation of β1 integrin activity by the CD2 antigen. J Cell Biol 1995;131:1867–1880.

    Article  PubMed  CAS  Google Scholar 

  58. Samelson LE, Fletcher MC, Ledbetter JA, June CH: Activation of tyrosine phospholylation in human T cells via the CD2 pathway: regulation by the CD45 tyrosine phosphatase. J Immunol 1990; 145;2448–2454.

    PubMed  CAS  Google Scholar 

  59. Weiss MJ, Daley JF, Hodgdon JC, Reinherz EL: Calcium dependency of antigen-specific (T3-Ti) and alternative (T11) pathways of human T-cell activation. Proc Natl Acad Sci USA 1984;81:6836–6840.

    Article  PubMed  CAS  Google Scholar 

  60. Hahn WC, Rosenstein Y, Burakoff SJ, Bierer BE: Interaction of CD2 with its ligand lymphocyte function-associated antigen-3 induces adenosine 3′,5′-cyclic monophosphate production in T lymphocytes. J Immunol 1991;147:14–21.

    PubMed  CAS  Google Scholar 

  61. Pantaleo G, Olive D, Poggi A, Kozumbo WJ, Moretta L, Moretta A: Transmembrane signalling via the T11-dependent pathway of human T cell activation. Evidence for the involvement of 1,2 diacylglycerol and inositol phosphates. Eur J Immunol 1987;17:55–60.

    Article  PubMed  CAS  Google Scholar 

  62. Bagnasco M, Nunes J, Lopez M, Cerdan C, Pierres A, Mawas C, Olive D: T cell activation via the CD2 molecule is associated with protein kinase C translocation from the cytosol to the plasma membrane. Eur J Immunol 1989; 19:823–827.

    Article  PubMed  CAS  Google Scholar 

  63. Kivens WJ, Hunt SW, III, Mobley L, Zeil T, Dell CL, Bierer BE, Shimizu Y: Identification of a proline-rich sequence in the CD2 cytoplasmic domain critical for regulation of integrin-mediated adhesion and activation of phosphoinositide 3-kinase. Mol Cell Biol 1998;18:5291–5307.

    PubMed  CAS  Google Scholar 

  64. Danielian S, Fagard R, Alcover A, Acuto O, Fischer S: The tyrosine kinase activity of p56lck is increased in human T cells activated via CD2. Eur J Immunol 1991;21:1967–1970.

    Article  PubMed  CAS  Google Scholar 

  65. Marie-Cardine A, Fischer S, Gorvel JP, Maridonneau-Parini I: Recruitment of activated p56lck on endosomes of CD2-triggered T cells, colocalization with ZAP-70. J Biol Chem 1996;271:20,734–20,739.

    Article  CAS  Google Scholar 

  66. King PD, Sadra A, Han A, Liu JR, Sunder-Plassmann R, Reinherz EL, Dupont B: CD2 signaling in T cells involves tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK. Int Immunol 1996;8:1707–1714.

    Article  PubMed  CAS  Google Scholar 

  67. King PD, Sadra A, Teng JM, Bell GM, Dupont B: CD2-mediated activation of the Tec-family tyrosine kinase ITK is controlled by proline-rich stretch-4 of the CD2 cytoplasmic tail. Int Immunol 1998; 10:1009–1016.

    Article  PubMed  CAS  Google Scholar 

  68. Lin HM, Hutchcroft JE, Andoniou CE, Kamoun M, Band H, Bierer BE: Association of p59fyn with the T lymphocyte costimulatory receptor CD2 binding of the Fyn Src homology (SH) 3 domain is regulated by the Fyn SH2 domain. J Biol Chem 1998;273:19,914–19,921.

    CAS  Google Scholar 

  69. Nel AE, Ledbetter IA, Williams K, Ho P, Akerley B, Franklin K, Katz R: Activation of MAP-2 kinase activity by the CD2 receptor in Jurkat T cells can be reversed by CD45 phosphatase. Immunology 1991;73:129–133.

    PubMed  CAS  Google Scholar 

  70. Graves JD, Downward J, Rayter S, Warne P, Tutt AL, Glennie M, Cantrell DA: CD2 antigen mediated activation of the guanine nucleotide binding proteins p21ras in human T lymphocytes. J Immunol 1991;146:3709–3712.

    PubMed  CAS  Google Scholar 

  71. Bierer BE, Hahn WC: T cell adhesion, avidity regulation and signaling: a molecular analysis of CD2. Semin Immunol 1993;5:249–261.

    Article  PubMed  CAS  Google Scholar 

  72. Chang H-C, Moingeon P, Pedersen R, Lucich J, Stebbins C, Reinherz EL: Involvement of the PPPGHR motif in T cell activation via CD2. J Exp Med 1990;172:351–354.

    Article  PubMed  CAS  Google Scholar 

  73. Cohen GB, Ren R, Baltimore D: Modular binding domains in signal transduction proteins. Cell 1995;80:237–248.

    Article  PubMed  CAS  Google Scholar 

  74. Bell GM, Fargnoli J, Bolen JB, Kish L, Imboden JB: The SH3 domain of p56lck binds to prolinerich sequences in the cytoplasmic domain of CD2. J Exp Med 1996; 183:169–178.

    Article  PubMed  CAS  Google Scholar 

  75. Bell GM, Bolen JB, Imboden JB: Association of Src-like protein tyrosine kinases with the CD2 cell surface molecule in rat T lymphocytes and natural killer cells. Mol Cell Biol 1992;12:5548–5554.

    PubMed  CAS  Google Scholar 

  76. Carmo AM, Mason DW, Beyers AD: Physical association of the cytoplasmic domain of CD2 with the tyrosine kinases p56lck and p59fyn. Eur J Immunol 1993;23: 2196–2201.

    Article  PubMed  CAS  Google Scholar 

  77. Beyers AD, Spruyt LL, Williams AF: Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5. Proc Natl Acad Sci USA 1992;89:2945–2949.

    Article  PubMed  CAS  Google Scholar 

  78. Gassmann M, Amrein KE, Flint NA, Schraven B, Burn P: Identification of a signaling complex involving CD2, ζ chain and p59fyn in T lymphocytes. Eur J Immunol 1994;24:139–144.

    Article  PubMed  CAS  Google Scholar 

  79. Hanke JH, Gardner JP, Dow RL, Changelian PS, Brissette WH, Weringer EJ, Pollok K, Connelly PA: Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor study of Lckand FynT-dependent T cell activation. J Biol Chem 1996:271:695–701.

    Article  PubMed  CAS  Google Scholar 

  80. Siliciano JD, Morrow TA, Desiderio SV:itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2. Proc Natl Acad Sci USA 1992;89:11,194–11,198.

    Article  CAS  Google Scholar 

  81. August A, Sadra A, Dupont B, Hanafusa H: Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the pleckstrin homology domain of inducible T cell kinase. Proc Natl Acad Sci USA 1997;94:11,227–11,232.

    Article  CAS  Google Scholar 

  82. Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S, Desai N, Widder P, Rosenberger F, Van der Merwe PA, Allen PM, Shaw AS: A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell 1998;94:667–677.

    Article  PubMed  CAS  Google Scholar 

  83. Cantrell D: T cell antigen receptor signal transduction pathways. Annu Rev Immunol 1996;14:259–274.

    Article  PubMed  CAS  Google Scholar 

  84. Qian DP, Weiss A: T cell antigen receptor signal transduction. Curr Opin Cell Biol 1997;9:205–212.

    Article  PubMed  CAS  Google Scholar 

  85. Cambier JC: Antigen and Fc receptor signaling. The awesome power of the immunoreceptor tyrosine-based activation motif. J Immunol 1995;155:3281–3285.

    PubMed  CAS  Google Scholar 

  86. Sussman JJ, Bonifacino JS, Lippincott-Schwartz J, Weissman AM, Saito T, Klausner RD, Ashwell JD: Failure to synthesize the T cell CD3-ζ chain: structure and function of a partial T cell receptor complex. Cell 1988;52:85–95.

    Article  PubMed  CAS  Google Scholar 

  87. Wegener A-MK, Letourneur F, Hoeveler A, Brocker T, Luton F, Malissen B: The T cell receptor/ CD3 complex is composed of at least two autonomous transduction modules. Cell 1992;68:83–95.

    Article  PubMed  CAS  Google Scholar 

  88. Letourneur F, Klausner RD: Activation of T cells by a tyrosine kinase activation domain in the cytoplasmic tail of CD3 ε. Science 1992;255:79–82.

    Article  PubMed  CAS  Google Scholar 

  89. Shinkai Y, Ma A, Cheng HL, Alt FW: CD3 e and CD3 ζ cytoplasmic domains can independently generate signals for T cell development and function. Immunity 1995;2:401–411.

    Article  PubMed  CAS  Google Scholar 

  90. Frank SJ, Niklinska BB, Orloff DG, Mercep M, Ashwell JD, Klausner RD: Structural mutations of the T cell receptor ζ chain and its role in T cell activation. Science 1990;249:174–177.

    Article  PubMed  CAS  Google Scholar 

  91. Wegener A-MK, Malissen B: Analysis of the (YXXL/I)2 signalling motifs found in the cytoplasmic segment of the mouse CD3-ζ chain. Adv Exp Med Biol 1994;365:45–51.

    PubMed  CAS  Google Scholar 

  92. Combadiere B, Freedman B, Chen L, Shores EW, Love P, Lenardo MJ: Qualitative and quantitative contributions of the T cell receptor ζ chain to mature T cell apoptosis. J Exp Med 1996;183:2109–2117.

    Article  PubMed  CAS  Google Scholar 

  93. Romeo C, Seed B: Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides. Cell 1991;64:1037–1046.

    Article  PubMed  CAS  Google Scholar 

  94. Irving BA, Weiss A: The cytoplasmic domain of the T cell receptor ζ chain is sufficient to couple to receptor-associated signal transduction pathways. Cell 1991;64:891–901.

    Article  PubMed  CAS  Google Scholar 

  95. Romeo C, Amiot M, Seed B: Sequence requirements for induction of cytolysis by the T cell antigen/ Fc receptor ζ chain. Cell 1992;68: 889–897.

    Article  PubMed  CAS  Google Scholar 

  96. Weiss A, Littman DR: Signal transduction by lymphocyte antigen receptors. Cell 1994;76:263–274.

    Article  PubMed  CAS  Google Scholar 

  97. Chan AC, Shaw AS: Regulation of antigen receptor signal transduction by protein tyrosine kinases. Curr Opin Immunol 1996; 8:394–401.

    Article  PubMed  CAS  Google Scholar 

  98. Wange RL, Samelson LE: Complex complexes: signaling at the TCR. Immunity 1996;5:197–205.

    Article  PubMed  CAS  Google Scholar 

  99. Songyang Z, Shoelson SE, Chandhuri M, Gish G, Pawson T, Haser WG, et al.: SH2 domains recognize specific phosphopeptide sequences. Cell 1993;72:767–778.

    Article  PubMed  CAS  Google Scholar 

  100. Songyang Z, Shoelson SE, McGlade J, Olivier P, Pawson T, Bustelo XR, Barbacid M, Sabe H, Hanafusa H, Yi T: Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Mol Cell Biol 1994; 14:2777–2785.

    PubMed  CAS  Google Scholar 

  101. Zhang WG, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE: LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell 1998;92:83–92.

    Article  PubMed  CAS  Google Scholar 

  102. van Kooyk Y, Weder P, Heije K, De Waal Malefijt R, Figdor CG: Role of intracellular Ca2+ levels in the regulation of CD11a/CD18 mediated cell adhesion. Cell Adhes Commun 1993;l:21–32.

    Article  Google Scholar 

  103. Hauss P, Mazerolles F, Hivroz C, Lecomte O, Barbat C, Fischer A: GF109203X, a specific PKC inhibitor, abrogates anti-CD3 antibody-induced upregulation of CD4+ T cell adhesion to B cells. Cell Immunol 1993;150:439–446.

    Article  PubMed  CAS  Google Scholar 

  104. Pardi R, Inverardi L, Rugarli C, Bender JR: Antigen-receptor complex stimulation triggers protein kinase C-dependent CD1la/CDl8-cytoskeleton association in T lymphocytes. J Cell Biol 1992;116: 1211–1220.

    Article  PubMed  CAS  Google Scholar 

  105. Kupfer A, Singer SJ: The specific interaction of helper T cells and antigen-presenting B cells. IV. Membrane and cytoskeletal reorganizations in the bound T cell as a function of antigen dose. J Exp Med 1989;170:1697–1714.

    Article  PubMed  CAS  Google Scholar 

  106. Jakubowski A, Rosa MD, Bixler S, Lobb R, Burkly LC: Vascular cell adhesion molecule (VCAM)-Ig fusion protein defines distinct affinity states of the very late antigen-4 (VLA-4) receptor. Cell Adhes Commun 1995;3:131–142.

    Article  PubMed  CAS  Google Scholar 

  107. Downward J, Graves JD, Warne PH, Rayter S, Cantrell DA: Stimulation of p21ras upon T-cell activation. Nature 1990;346:719–712.

    Article  PubMed  CAS  Google Scholar 

  108. Mobley JL, Ennis E, Shimizu Y: Isolation and characterization of cell lines with genetically distinct mutations downstream of protein kinase C that result in defective activation-dependent regulation of T cell integrin function. J Immunol 1996;156:948–956.

    PubMed  CAS  Google Scholar 

  109. O’Rourke AM, Shao H, Kaye J: Cutting edge: a role for p21ras/ MAP kinase in TCR-mediated activation of LFA-1. J Immunol 1998;161:5800–5803.

    PubMed  CAS  Google Scholar 

  110. Rodriguez-Viciana P, Warne PH, Khwaja A, Marte BM, Pappin D, Das P, Waterfield MD, Ridley A, Downward J: Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras. Cell 1997; 89:457–467.

    Article  PubMed  CAS  Google Scholar 

  111. Zhang ZH, Vuori K, Wang HG, Reed JC, Ruoslahti E: Integrin activation by R-ras. Cell 1996;85:61–69.

    Article  PubMed  CAS  Google Scholar 

  112. Marte BM, Rodriguez-Viciana P, Wennström S, Warne PH, Downward J: R-Ras can activate the phosphoinositide 3-kinase but not the MAP kinase arm of the Ras effector pathways. Curr Biol 1997;7:63–70.

    Article  PubMed  CAS  Google Scholar 

  113. Shimizu Y, Hunt SW, III: Regulating integrin-mediated adhesion: one more function for PI 3-kinase? Immunol Today 1996;17:565–573.

    Article  PubMed  CAS  Google Scholar 

  114. Exley M, Varticovski L, Peter M, Sancho J, Terhorst C: Association of phosphatidylinositol 3-kinase with a specific sequence of the T cell receptor ζ chain is dependent on T cell activation. J Biol Chem 1994;269:15,140–15,146.

    CAS  Google Scholar 

  115. Osman N, Turner H, Lucas S, Reif K, Cantrell DA: The protein interactions of the immunoglobulin receptor family tyrosine-based activation motifs present in the T cell receptor ζ subunit and the CD3 ζ, δ, and ε chains. Eur J Immunol 1996;26:1063–1068.

    Article  PubMed  CAS  Google Scholar 

  116. De Aós I, Metzger MH, Exley M, Dahl CE, Misra S, Zheng DX, Varticovski L, Terhorst C, Sancho J: Tyrosine phosphory lation of the CD3-ε subunit of the T cell antigen receptor mediates enhanced association with phosphatidylinositol 3-kinase in Jurkat T cells. J Biol Chem 1997;272:25,310–25,318.

    Google Scholar 

  117. Clark MR, Campbell KS, Kazlauskas A, Johnson SA, Hertz M, Potter TA, Pleiman C, Cambier JC: The B cell antigen receptor complex: association of Ig-α and Ig-β with distinct cytoplasmic effectors. Science 1992;258:123–126.

    Article  PubMed  CAS  Google Scholar 

  118. Tuscano JM, Engel P, Tedder TF, Agarwal A, Kehrl JH: Involvement of p72syk kinase, p53/56lyn kinase and phosphatidyl inositol3 kinase in signal transduction via the human B lymphocyte antigen CD22. Eur J Immunol 1996;26: 1246–1252.

    Article  PubMed  CAS  Google Scholar 

  119. Ward SG, June CH, Olive D: PI 3-kinase: a pivotal pathway in T-cell activation? Immunol Today 1996; 17:187–197.

    Article  PubMed  CAS  Google Scholar 

  120. Stein PH, Fraser JD, Weiss A: The cytoplasmic domain of CD28 is both necessary and sufficient for costimulation of interleukin-2 secretion and association with phosphatidylinositol 3′-kinase. Mol Cell Biol 1994; 14:3392–3402.

    PubMed  CAS  Google Scholar 

  121. Fukazawa T, Reedquist KA, Panchamoorthy G, Soltoff S, Trub T, Druker B, Cantley L, Shoelson SE, Band H: T cell activation-dependent association between the p85 subunit of the phosphatidylinositol 3-kinase and Grb2/phospholipase C-gl-binding phosphotyrosyl protein pp36/38. J Biol Chem 1995;270:20,177–20,182.

    CAS  Google Scholar 

  122. Downward J: Role of phosphoinositide-3-OH kinase in Ras signaling. Adv Second Messenger Phosphoprotein Res 1997;31:1–10.

    PubMed  CAS  Google Scholar 

  123. Bruyns E, Marie-Cardine A, Kirchgessner H, Sagolla K, Shevchenko A, Mann M, Autschbach F, Bensussan A, Meuer S, Schraven B: T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-ζ complex, recruits intracellular signaling proteins to the plasma membrane. J Exp Med 1998;188:561–575.

    Article  PubMed  CAS  Google Scholar 

  124. Kolanus W, Nagel W, Schiller B, Zeitlmann L, Godar S, Stockinger H, Seed B: αLβ2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin1, a cytoplasmic regulatory molecule. Cell 1996;86:233–242.

    Article  PubMed  CAS  Google Scholar 

  125. Klarlund JK, Guilherme A, Holik JJ, Virbasius JV, Chawla A, Czech MP: Signaling by phosphoinositide-3,4,5 -trisphosphate through proteins containing pleckstrin and Sec7 homology domains. Science 1997;275:1927–1930.

    Article  PubMed  CAS  Google Scholar 

  126. Le Good JA, Ziegler WH, Parekh DB, Alessi DR, Cohen P, Parker PJ: Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. Science 1998;281:2042–2045.

    Article  PubMed  Google Scholar 

  127. Chou MM, Hou WM, Johnson J, Graham LK, Lee MH, Chen CS, Newton AC, Schaffhausen BS, Toker A: Regulation of protein kinase C ζ by PI 3-kinase and PDK-1. Curr Biol 1998;8:1069–1077.

    Article  PubMed  CAS  Google Scholar 

  128. D’Souza-Schorey C, Boettner B, Van Aelst L: Rac regulates integrin-mediated spreading and increased adhesion of T lymphocytes. Mol Cell Biol 1998;18: 3936–3946.

    PubMed  CAS  Google Scholar 

  129. Michiels F, Stam JC, Hordijk PL, Van der Kammen RA, Ruuls-Van Stalle L, Feltkamp CA, Collard JG: Regulated membrane localization of Tiam 1, mediated by the NH2-terminal pleckstrin homology domain, is required for Racdependent membrane ruffling and c-jun NH2-terminal kinase activation. J Cell Biol 1997;137:387–398.

    Article  PubMed  CAS  Google Scholar 

  130. Stam JC, Sander EE, Michiels F, Van Leeuwen FN, Kain HET, Van der Kammen RA, Collard JG: Targeting of Tiam1 to the plasma membrane requires the cooperative function of the N-terminal pleckstrin homology domain and an adjacent protein interaction domain. J Biol Chem 1997;272: 28,447–28,454.

    Article  CAS  Google Scholar 

  131. Sander EE, van Delft S, ten Klooster JP, Reid T, Van der Kammen RA, Michiels F, Collard JG: Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. J Cell Biol 1998;143:1385–1398.

    Article  PubMed  CAS  Google Scholar 

  132. Roach TI, Slater SE, White LS, Zhang XL, Majerus PW, Brown EJ, Thomas ML: The protein tyrosine phosphatase SHP-1 regulates integrin-mediated adhesion of macrophages. Curr Biol 1998; 8:1035–1038.

    Article  PubMed  CAS  Google Scholar 

  133. Helgason CD, Damen JE, Rosten P, Grewal R, Sorenson P, Chappel SM, Borowski A, Jirik F, Krystal G, Humphries RK: Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span. Genes Dev 1998;12:1610–1620.

    PubMed  CAS  Google Scholar 

  134. Tamura M, Gu J, Matusmoto K, Aota S, Parsons R, Yamada KM: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 1998;280:1614–1617.

    Article  PubMed  CAS  Google Scholar 

  135. Gu J, Tamura M, Yamada KM: Tumor suppressor PTEN inhibits integrinand growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways. J Cell Biol 1998;143:1375–1383.

    Article  PubMed  CAS  Google Scholar 

  136. Maehama T, Dixon JE: The tumor suppressor, PTEN/ MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5trisphosphate. J Biol Chem 1998;273:13,375–13,378.

    Article  CAS  Google Scholar 

  137. Serve H, Yee NS, Stella G, Sepp-Lorenzino L, Tan JC, Besmer P: Differential roles of PI 3-kinase and kit tyrosine 821 in kit receptor-mediated proliferation, survival and cell adhesion in mast cells. EMBO J 1995;14:473–483.

    PubMed  CAS  Google Scholar 

  138. Kinashi T, Springer TA: Steel factor and c-kit regulate cellmatrix adhesion. Blood 1994;83:1033–1038.

    PubMed  CAS  Google Scholar 

  139. Vosseller K, Stella G, Yee NS, Besmer P: c-Kit receptor signaling through its phosphatidylinositide3′-kinase-binding site and protein kinase C: role in mast cell enhancement of degranulation, adhesion, and membrane ruffling. Mol Biol Cell 1997;8:909–922.

    PubMed  CAS  Google Scholar 

  140. Kinashi T, Escobedo JA, Williams LT, Takatsu K, Springer TA: Receptor tyrosine kinase stimulates cell-matrix adhesion by phosphatidylinositol 3 kinase and phospholipase C-γ1 pathways. Blood 1995;86: 2086–2090.

    PubMed  CAS  Google Scholar 

  141. Adelsman MA, McCarthy JB, Shimizu Y: Stimulation of β1 integrin function by epidermal growth factor and heregulin-β has distinct requirements for erbB2 but a similar dependence on PI 3-kinase. Mol Biol Cell 1999; In press.

  142. Jones SL, Knaus UG, Bokoch GM, Brown EJ: Two signaling mechanisms for activation of αMβ2 avidity in polymorphonuclear neutrophils. J Biol Chem 1998;273:10,556–10,566.

    CAS  Google Scholar 

  143. Zauli G, Bassini A, Vitale M, Gibellini D, Celeghini C, Caramelli E, Pierpaoli S, Guidotti L, Capitani S: Thrombopoietin enhances the αIIbβ3-dependent adhesion of megakaryocytic cells to fibrinogen or fibronectin through PI 3 kinase. Blood 1997;89:883–895.

    PubMed  CAS  Google Scholar 

  144. Turner L, Ward SG, Westwick J: RANTES-activated human T lymphocytes. A role for phosphoinosiude 3-kinase. J Immunol 1995;155:2437–2444.

    PubMed  CAS  Google Scholar 

  145. Laudanna C, Mochly-Rosen D, Liron T, Constantin G, Butcher EC: Evidence of ζ protein kinase C involvement in polymorphonuclear neutrophil integrin-dependent adhesion and chemotaxis. J Biol Chem 1998;273:30,306–30,315.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN

    Traci Zeil, Wendy J. Kivens, Sirid-Aimée Kellermann & Yoji Shimizu Ph.D.

  2. Dept. Lab. Med. Path., Univ. Minn. Med. School, Box 334 Mavo/6, 266, BSBE

    Yoji Shimizu Ph.D.

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  1. Traci Zeil
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Zeil, T., Kivens, W.J., Kellermann, SA. et al. Regulation of integrin function by T cell activation. Immunol Res 20, 127–145 (1999). https://doi.org/10.1007/BF02786469

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