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Regulation of T cell integrin function by adapter proteins

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Abstract

Integrins are cell surface heterodimers that bind adhesion molecules expressed on other cells or in the extracellular matrix. Integrin-mediated interactions are critical for T cell development in the thymus, migration of T cells in the periphery, and induction of T cell effector functions. In resting T cells, integrins are maintained in a low affinity state. Engagement of the T cell receptor or chemokine receptors increases integrin affinity, enabling integrins to bind their ligands and initiate a signaling cascade resulting in altered cell morphology and motility. Our laboratory is interested how adapter proteins, mediators of intracellular signal transduction, regulate both signals from the T cell receptor to integrins (inside-out signaling) and (outside-in) signals from integrins into the cell.

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References

  1. Luo BH, Carman CV, Springer TA. Structural basis of integrin regulation and signaling. Annu Rev Immunol. 2007;25:619–47.

    Article  PubMed  CAS  Google Scholar 

  2. Takagi J, Petre BM, Walz T, Springer TA. Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell. 2002;110:599–11.

    Article  PubMed  CAS  Google Scholar 

  3. Shimaoka M, Xiao T, Liu JH, Yang Y, Dong Y, Jun CD, et al. Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell. 2003;112:99–111.

    Article  PubMed  CAS  Google Scholar 

  4. 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;97:2139–44.

    Article  PubMed  CAS  Google Scholar 

  5. Cambi A, Joosten B, Koopman M, de Lange F, Beeren I, Torensma R, et al. Organization of the integrin LFA-1 in nanoclusters regulates its activity. Mol Biol Cell. 2006;17:4270–81.

    Article  PubMed  CAS  Google Scholar 

  6. Cairo CW, Mirchev R, Golan DE. Cytoskeletal regulation couples LFA-1 conformational changes to receptor lateral mobility and clustering. Immunity. 2006;25:297–308.

    Article  PubMed  CAS  Google Scholar 

  7. Mor A, Dustin ML, Philips MR. Small GTPases and LFA-1 reciprocally modulate adhesion and signaling. Immunol Rev. 2007;218:114–25.

    Article  PubMed  CAS  Google Scholar 

  8. Bunnell SC, Hong DI, Kardon JR, Yamazaki T, McGlade CJ, Barr VA, et al. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J Cell Biol. 2002;158:1263–75.

    Article  PubMed  CAS  Google Scholar 

  9. Goda S, Quale AC, Woods ML, Felthauser A, Shimizu Y. Control of TCR-mediated activation of beta 1 integrins by the ZAP-70 tyrosine kinase interdomain B region and the linker for activation of T cells adapter protein. J Immunol. 2004;172:5379–87.

    PubMed  CAS  Google Scholar 

  10. Katagiri K, Shimonaka M, Kinashi T. Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1. J Biol Chem. 2004;279:11875–81.

    Article  PubMed  CAS  Google Scholar 

  11. Dustin ML, Springer TA. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989;341:619–24.

    Article  PubMed  CAS  Google Scholar 

  12. Shimizu Y, Newman W, Gopal TV, Horgan KJ, Graber N, Beall LD, et al. Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions. J Cell Biol. 1991;113:1203–12.

    Article  PubMed  CAS  Google Scholar 

  13. Rozengurt E, Rey O, Waldron RT. Protein kinase D signaling. J Biol Chem. 2005;280:13205–8.

    Article  PubMed  CAS  Google Scholar 

  14. Koretzky GA, Abtahian F, Silverman MA. SLP76 and SLP65: complex regulation of signalling in lymphocytes and beyond. Nat Rev Immunol. 2006;6:67–78.

    Article  PubMed  CAS  Google Scholar 

  15. Singer AL, Bunnell SC, Obstfeld AE, Jordan MS, Wu JN, Myung PS, et al. Roles of the proline-rich domain in SLP-76 subcellular localization and T cell function. J Biol Chem. 2004;279:15481–90.

    Article  PubMed  CAS  Google Scholar 

  16. Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, et al. Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol. 2005;6:1253–62.

    Article  PubMed  CAS  Google Scholar 

  17. Bunnell SC, Kapoor V, Trible RP, Zhang W, Samelson LE. Dynamic actin polymerization drives T cell receptor-induced spreading: a role for the signal transduction adaptor LAT. Immunity. 2001;14:315–29.

    Article  PubMed  CAS  Google Scholar 

  18. Myung PS, Derimanov GS, Jordan MS, Punt JA, Liu QH, Judd BA, et al. Differential requirement for SLP-76 domains in T cell development and function. Immunity. 2001;15:1011–26.

    Article  PubMed  CAS  Google Scholar 

  19. Jordan MS, Sadler J, Austin JE, Finkelstein LD, Singer AL, Schwartzberg PL, et al. Functional hierarchy of the N-terminal tyrosines of SLP-76. J Immunol. 2006;176:2430–8.

    PubMed  CAS  Google Scholar 

  20. Finkelstein LD, Shimizu Y, Schwartzberg PL. Tec kinases regulate TCR-mediated recruitment of signaling molecules and integrin-dependent cell adhesion. J Immunol. 2005;175:5923–30.

    PubMed  CAS  Google Scholar 

  21. Gomez TS, Kumar K, Medeiros RB, Shimizu Y, Leibson PJ, Billadeau DD. Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity. 2007;26:177–90.

    Article  PubMed  CAS  Google Scholar 

  22. Krawczyk C, Oliveira-dos-Santos A, Sasaki T, Griffiths E, Ohashi PS, Snapper S, et al. Vav1 controls integrin clustering and MHC/peptide-specific cell adhesion to antigen-presenting cells. Immunity. 2002;16:331–43.

    Article  PubMed  CAS  Google Scholar 

  23. Fischer KD, Kong YY, Nishina H, Tedford K, Marengere LE, Kozieradzki I, et al. Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor. Curr Biol. 1998;8:554–62.

    Article  PubMed  CAS  Google Scholar 

  24. Fischer KD, Zmuldzinas A, Gardner S, Barbacid M, Bernstein A, Guidos C. Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes. Nature. 1995;374:474–7.

    Article  PubMed  CAS  Google Scholar 

  25. Jordan MS, Smith JE, Burns JC, Austin JE, Nichols KE, Aschenbrenner AC, et al. Complementation in trans of altered thymocyte development in mice expressing mutant forms of the adaptor molecule SLP76. Immunity. 2008;28:359–69.

    Article  PubMed  CAS  Google Scholar 

  26. Zeng R, Cannon JL, Abraham RT, Way M, Billadeau DD, Bubeck-Wardenberg J, et al. SLP-76 coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/Cdc42-dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact site. J Immunol. 2003;171:1360–8.

    PubMed  CAS  Google Scholar 

  27. Snapper SB, Rosen FS, Mizoguchi E, Cohen P, Khan W, Liu CH, et al. Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity. 1998;9:81–91.

    Article  PubMed  CAS  Google Scholar 

  28. Sims TN, Soos TJ, Xenias HS, Dubin-Thaler B, Hofman JM, Waite JC, et al. Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse. Cell. 2007;129:773–85.

    Article  PubMed  CAS  Google Scholar 

  29. Badour K, Zhang J, Shi F, McGavin MK, Rampersad V, Hardy LA, et al. The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse. Immunity. 2003;18:141–54.

    Article  PubMed  CAS  Google Scholar 

  30. Cannon JL, Burkhardt JK. Differential roles for Wiskott-Aldrich syndrome protein in immune synapse formation and IL-2 production. J Immunol. 2004;173:1658–62.

    PubMed  CAS  Google Scholar 

  31. Musci MA, Hendricks-Taylor LR, Motto DG, Paskind M, Kamens J, Turck CW, et al. Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases. J Biol Chem. 1997;272:11674–7.

    Article  PubMed  CAS  Google Scholar 

  32. Geng L, Raab M, Rudd CE. Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651. J Immunol. 1999;163:5753–7.

    PubMed  CAS  Google Scholar 

  33. Raab M, Kang H, da Silva A, Zhu X, Rudd CE. FYN-T-FYB-SLP-76 interactions define a T-cell receptor zeta/CD3-mediated tyrosine phosphorylation pathway that up-regulates interleukin 2 transcription in T-cells. J Biol Chem. 1999;274:21170–9.

    Article  PubMed  CAS  Google Scholar 

  34. Peterson EJ, Woods ML, Dmowski SA, Derimanov G, Jordan MS, Wu JN, et al. Coupling of the TCR to integrin activation by Slap-130/Fyb. Science. 2001;293:2263–5.

    Article  PubMed  CAS  Google Scholar 

  35. Griffiths EK, Krawczyk C, Kong YY, Raab M, Hyduk SJ, Bouchard D, et al. Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap. Science. 2001;293:2260–3.

    Article  PubMed  CAS  Google Scholar 

  36. Krause M, Sechi AS, Konradt M, Monner D, Gertler FB, Wehland J. Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton. J Cell Biol. 2000;149:181–94.

    Article  PubMed  CAS  Google Scholar 

  37. Kasirer-Friede A, Moran B, Nagrampa-Orje J, Swanson K, Ruggeri ZM, Schraven B, et al. ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other agonists. Blood. 2007;109:1018–25.

    Article  PubMed  CAS  Google Scholar 

  38. Duke-Cohan JS, Kang H, Liu H, Rudd CE. Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein. J Biol Chem. 2006;281:13743–50.

    Article  PubMed  CAS  Google Scholar 

  39. Marie-Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer SC, Schraven B. Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes. J Biol Chem. 1997;272:16077–80.

    Article  PubMed  CAS  Google Scholar 

  40. Kang H, Freund C, Duke-Cohan JS, Musacchio A, Wagner G, Rudd CE. SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55. EMBO J. 2000;19:2889–99.

    Article  PubMed  CAS  Google Scholar 

  41. Huang Y, Norton DD, Precht P, Martindale JL, Burkhardt JK, Wange RL. Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells. J Biol Chem. 2005;280:23576–83.

    Article  PubMed  CAS  Google Scholar 

  42. Marie-Cardine A, Hendricks-Taylor LR, Boerth NJ, Zhao H, Schraven B, Koretzky GA. Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130. J Biol Chem. 1998;273:25789–95.

    Article  PubMed  CAS  Google Scholar 

  43. Wang H, McCann FE, Gordan JD, Wu X, Raab M, Malik TH, et al. ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC conjugation. J Exp Med. 2004;200:1063–74.

    Article  PubMed  CAS  Google Scholar 

  44. Menasche G, Kliche S, Chen EJ, Stradal TE, Schraven B, Koretzky G. RIAM links the ADAP/SKAP-55 signaling module to Rap1, facilitating T-cell-receptor-mediated integrin activation. Mol Cell Biol. 2007;27:4070–81.

    Article  PubMed  CAS  Google Scholar 

  45. Lafuente EM, van Puijenbroek AA, Krause M, Carman CV, Freeman GJ, Berezovskaya A, et al. RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion. Dev Cell. 2004;7:585–95.

    Article  PubMed  CAS  Google Scholar 

  46. Sebzda E, Bracke M, Tugal T, Hogg N, Cantrell DA. Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling. Nat Immunol. 2002;3:251–8.

    Article  PubMed  CAS  Google Scholar 

  47. Huang CC, You JL, Wu MY, Hsu KS. Rap1-induced p38 mitogen-activated protein kinase activation facilitates AMPA receptor trafficking via the GDI.Rab5 complex. Potential role in (S)-3,5-dihydroxyphenylglycine-induced long term depression. J Biol Chem. 2004;279:12286–92.

    Article  PubMed  CAS  Google Scholar 

  48. Katagiri K, Hattori M, Minato N, Irie S, Takatsu K, Kinashi T. Rap1 is a potent activation signal for leukocyte function-associated antigen 1 distinct from protein kinase C and phosphatidylinositol-3-OH kinase. Mol Cell Biol. 2000;20:1956–69.

    Article  PubMed  CAS  Google Scholar 

  49. Duchniewicz M, Zemojtel T, Kolanczyk M, Grossmann S, Scheele JS, Zwartkruis FJ. Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion. Mol Cell Biol. 2006;26:643–53.

    Article  PubMed  CAS  Google Scholar 

  50. Bivona TG, Wiener HH, Ahearn IM, Silletti J, Chiu VK, Philips MR. Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion. J Cell Biol. 2004;164:461–70.

    Article  PubMed  CAS  Google Scholar 

  51. Medeiros RB, Dickey DM, Chung H, Quale AC, Nagarajan LR, Billadeau DD, et al. Protein kinase D1 and the beta 1 integrin cytoplasmic domain control beta 1 integrin function via regulation of Rap1 activation. Immunity. 2005;23:213–26.

    Article  PubMed  CAS  Google Scholar 

  52. Kliche S, Breitling D, Togni M, Pusch R, Heuer K, Wang X, et al. The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1. Mol Cell Biol. 2006;26:7130–44.

    Article  PubMed  CAS  Google Scholar 

  53. Katagiri K, Maeda A, Shimonaka M, Kinashi T. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat Immunol. 2003;4:741–8.

    Article  PubMed  CAS  Google Scholar 

  54. Han J, Lim CJ, Watanabe N, Soriani A, Ratnikov B, Calderwood DA, et al. Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3. Curr Biol. 2006;16:1796–806.

    Article  PubMed  CAS  Google Scholar 

  55. Tadokoro S, Shattil SJ, Eto K, Tai V, Liddington RC, de Pereda JM, et al. Talin binding to integrin beta tails: a final common step in integrin activation. Science. 2003;302:103–6.

    Article  PubMed  CAS  Google Scholar 

  56. Wegener KL, Partridge AW, Han J, Pickford AR, Liddington RC, Ginsberg MH, et al. Structural basis of integrin activation by talin. Cell. 2007;128:171–82.

    Article  PubMed  CAS  Google Scholar 

  57. Yan B, Calderwood DA, Yaspan B, Ginsberg MH. Calpain cleavage promotes talin binding to the beta 3 integrin cytoplasmic domain. J Biol Chem. 2001;276:28164–70.

    Article  PubMed  CAS  Google Scholar 

  58. Liu S, Thomas SM, Woodside DG, Rose DM, Kiosses WB, Pfaff M, et al. Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses. Nature. 1999;402:676–81.

    Article  PubMed  CAS  Google Scholar 

  59. Feigelson SW, Grabovsky V, Winter E, Chen LL, Pepinsky RB, Yednock T, et al. The Src kinase p56(lck) up-regulates VLA-4 integrin affinity. Implications for rapid spontaneous and chemokine-triggered T cell adhesion to VCAM-1 and fibronectin. J Biol Chem. 2001;276:13891–901.

    PubMed  CAS  Google Scholar 

  60. Patrussi L, Baldari CT. Intracellular mediators of CXCR4-dependent signaling in T cells. Immunol Lett. 2008;115:75–82.

    Article  PubMed  CAS  Google Scholar 

  61. Ticchioni M, Charvet C, Noraz N, Lamy L, Steinberg M, Bernard A, et al. Signaling through ZAP-70 is required for CXCL12-mediated T-cell transendothelial migration. Blood. 2002;99:3111–8.

    Article  PubMed  CAS  Google Scholar 

  62. Soede RD, Wijnands YM, Van Kouteren-Cobzaru I, Roos E. ZAP-70 tyrosine kinase is required for LFA-1-dependent T cell migration. J Cell Biol. 1998;142:1371–9.

    Article  PubMed  CAS  Google Scholar 

  63. Ottoson NC, Pribila JT, Chan AS, Shimizu Y. Cutting edge: T cell migration regulated by CXCR4 chemokine receptor signaling to ZAP-70 tyrosine kinase. J Immunol. 2001;167:1857–61.

    PubMed  CAS  Google Scholar 

  64. Patrussi L, Ulivieri C, Lucherini OM, Paccani SR, Gamberucci A, Lanfrancone L, et al. p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells. Blood. 2007;110:1730–8.

    Article  PubMed  CAS  Google Scholar 

  65. Kremer KN, Humphreys TD, Kumar A, Qian NX, Hedin KE. Distinct role of ZAP-70 and Src homology 2 domain-containing leukocyte protein of 76 kDa in the prolonged activation of extracellular signal-regulated protein kinase by the stromal cell-derived factor-1 alpha/CXCL12 chemokine. J Immunol. 2003;171:360–7.

    PubMed  CAS  Google Scholar 

  66. Okabe S, Tauchi T, Ohyashiki K, Broxmeyer HE. Stromal-cell-derived factor-1/CXCL12-induced chemotaxis of a T cell line involves intracellular signaling through Cbl and Cbl-b and their regulation by Src kinases and CD45. Blood Cells Mol Dis. 2006;36:308–14.

    Article  PubMed  CAS  Google Scholar 

  67. Bach TL, Chen QM, Kerr WT, Wang Y, Lian L, Choi JK, et al. Phospholipase cbeta is critical for T cell chemotaxis. J Immunol. 2007;179:2223–7.

    PubMed  CAS  Google Scholar 

  68. Garcia-Bernal D, Wright N, Sotillo-Mallo E, Nombela-Arrieta C, Stein JV, Bustelo XR, et al. Vav1 and Rac control chemokine-promoted T lymphocyte adhesion mediated by the integrin alpha4beta1. Mol Biol Cell. 2005;16:3223–35.

    Article  PubMed  CAS  Google Scholar 

  69. Shimonaka M, Katagiri K, Nakayama T, Fujita N, Tsuruo T, Yoshie O, et al. Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow. J Cell Biol. 2003;161:417–27.

    Article  PubMed  CAS  Google Scholar 

  70. Ghandour H, Cullere X, Alvarez A, Luscinskas FW, Mayadas TN. Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion. Blood. 2007;110:3682–90.

    Article  PubMed  CAS  Google Scholar 

  71. Katagiri K, Ohnishi N, Kabashima K, Iyoda T, Takeda N, Shinkai Y, et al. Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking. Nat Immunol. 2004;5:1045–51.

    Article  PubMed  CAS  Google Scholar 

  72. Ginsberg MH, Partridge A, Shattil SJ. Integrin regulation. Curr Opin Cell Biol. 2005;17:509–16.

    Article  PubMed  CAS  Google Scholar 

  73. de Virgilio M, Kiosses WB, Shattil SJ. Proximal, selective, and dynamic interactions between integrin alphaIIbbeta3 and protein tyrosine kinases in living cells. J Cell Biol. 2004;165:305–11.

    Article  PubMed  Google Scholar 

  74. Arias-Salgado EG, Lizano S, Sarkar S, Brugge JS, Ginsberg MH, Shattil SJ. Src kinase activation by direct interaction with the integrin beta cytoplasmic domain. Proc Natl Acad Sci USA. 2003;100:13298–302.

    Article  PubMed  CAS  Google Scholar 

  75. Obergfell A, Eto K, Mocsai A, Buensuceso C, Moores SL, Brugge JS, et al. Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton. J Cell Biol. 2002;157:265–75.

    Article  PubMed  CAS  Google Scholar 

  76. Abtahian F, Bezman N, Clemens R, Sebzda E, Cheng L, Shattil SJ, et al. Evidence for the requirement of ITAM domains but not SLP-76/Gads interaction for integrin signaling in hematopoietic cells. Mol Cell Biol. 2006;26:6936–49.

    Article  PubMed  CAS  Google Scholar 

  77. Woodside DG, Obergfell A, Talapatra A, Calderwood DA, Shattil SJ, Ginsberg MH. The N-terminal SH2 domains of Syk and ZAP-70 mediate phosphotyrosine-independent binding to integrin beta cytoplasmic domains. J Biol Chem. 2002;277:39401–8.

    Article  PubMed  CAS  Google Scholar 

  78. Woodside DG, Obergfell A, Leng L, Wilsbacher JL, Miranti CK, Brugge JS, et al. Activation of Syk protein tyrosine kinase through interaction with integrin beta cytoplasmic domains. Curr Biol. 2001;11:1799–804.

    Article  PubMed  CAS  Google Scholar 

  79. Mocsai A, Abram CL, Jakus Z, Hu Y, Lanier LL, Lowell CA. Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs. Nat Immunol. 2006;7:1326–33.

    Article  PubMed  CAS  Google Scholar 

  80. Judd BA, Myung PS, Obergfell A, Myers EE, Cheng AM, Watson SP, et al. Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signaling. J Exp Med. 2002;195:705–17.

    Article  PubMed  CAS  Google Scholar 

  81. Jordan MS, Maltzman JS, Kliche S, Shabason J, Smith JE, Obstfeld A, et al. In vivo disruption of T cell development by expression of a dominant-negative polypeptide designed to abolish the SLP-76/Gads interaction. Eur J Immunol. 2007;37:2961–72.

    Article  PubMed  CAS  Google Scholar 

  82. Hunter AJ, Ottoson N, Boerth N, Koretzky GA, Shimizu Y. Cutting edge: a novel function for the SLAP-130/FYB adapter protein in beta 1 integrin signaling and T lymphocyte migration. J Immunol. 2000;164:1143–7.

    PubMed  CAS  Google Scholar 

  83. Suzuki J, Yamasaki S, Wu J, Koretzky GA, Saito T. The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation. Blood. 2007;109:168–75.

    Article  PubMed  CAS  Google Scholar 

  84. Obergfell A, Judd BA, del Pozo MA, Schwartz MA, Koretzky GA, Shattil SJ. The molecular adapter SLP-76 relays signals from platelet integrin alphaIIbbeta3 to the actin cytoskeleton. J Biol Chem. 2001;276:5916–23.

    Article  PubMed  CAS  Google Scholar 

  85. Newbrough SA, Mocsai A, Clemens RA, Wu JN, Silverman MA, Singer AL, et al. SLP-76 regulates Fcgamma receptor and integrin signaling in neutrophils. Immunity. 2003;19:761–9.

    Article  PubMed  Google Scholar 

  86. Bezman NA, Lian L, Abrams CS, Brass LF, Kahn ML, Jordan MS, et al. Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo. J Exp Med. 2008;205:1775–88.

    Article  PubMed  CAS  Google Scholar 

  87. Nguyen K, Sylvain NR, Bunnell SC. T cell costimulation via the integrin VLA-4 inhibits the actin-dependent centralization of signaling microclusters containing the adaptor SLP-76. Immunity. 2008;28:810–21.

    Article  PubMed  CAS  Google Scholar 

  88. Clements JL, Yang B, Ross-Barta SE, Eliason SL, Hrstka RF, Williamson RA, et al. Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development. Science. 1998;281:416–9.

    Article  PubMed  CAS  Google Scholar 

  89. Maltzman JS, Kovoor L, Clements JL, Koretzky GA. Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection. J Exp Med. 2005;202:893–900.

    Article  PubMed  CAS  Google Scholar 

  90. Zarbock A, Lowell CA, Ley K. Spleen tyrosine kinase Syk is necessary for E-selectin-induced alpha(L)beta(2) integrin-mediated rolling on intercellular adhesion molecule-1. Immunity. 2007;26:773–83.

    Article  PubMed  CAS  Google Scholar 

  91. Kumar A, Humphreys TD, Kremer KN, Bramati PS, Bradfield L, Edgar CE, et al. CXCR4 physically associates with the T cell receptor to signal in T cells. Immunity. 2006;25:213–24.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Leonard and Madlyn Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    Rebecca G. Baker & Gary A. Koretzky

  2. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    Gary A. Koretzky

  3. Department of Medicine, University of Pennsylvania School of Medicine, 415 BRB II/III, 421 Curie Blvd., Philadelphia, PA, 19104, USA

    Gary A. Koretzky

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Correspondence to Gary A. Koretzky.

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Baker, R.G., Koretzky, G.A. Regulation of T cell integrin function by adapter proteins. Immunol Res 42, 132–144 (2008). https://doi.org/10.1007/s12026-008-8047-8

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