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. 1997 Nov 3;16(21):6414–6425. doi: 10.1093/emboj/16.21.6414

Regulation of the pp72syk protein tyrosine kinase by platelet integrin alpha IIb beta 3.

J Gao 1, K E Zoller 1, M H Ginsberg 1, J S Brugge 1, S J Shattil 1
PMCID: PMC1170248  PMID: 9351824

Abstract

pp72syk is essential for development and function of several hematopoietic cells, and it becomes activated through tandem SH2 interaction with ITAM motifs in immune response receptors. Since Syk is also activated through integrins, which do not contain ITAMs, a CHO cell model system was used to study Syk activation by the platelet integrin, alpha IIb beta 3. As in platelets, Syk underwent tyrosine phosphorylation and activation during CHO cell adhesion to alpha IIb beta 3 ligands, including fibrinogen. This involved Syk autophosphorylation and the tyrosine kinase activity of Src, and it exhibited two novel features. Firstly, unlike alpha IIb beta 3-mediated activation of pp125FAK, Syk activation could be triggered by the binding of soluble fibrinogen and abolished by truncation of the alpha IIb or beta 3 cytoplasmic tail, and it was resistant to inhibition by cytochalasin D. Secondly, it did not require phosphorylated ITAMs since it was unaffected by disruption of an ITAM-interaction motif in the SH2(C) domain of Syk or by simultaneous overexpression of the tandem SH2 domains. These studies demonstrate that Syk is a proximal component in alpha IIb beta 3 signaling and is regulated as a consequence of intimate functional relationships with the alpha IIb beta 3 cytoplasmic tails and with Src or a closely related kinase. Furthermore, there are fundamental differences in the activation of Syk by alpha IIb beta 3 and immune response receptors, suggesting a unique role for integrins in Syk function.

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Selected References

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  1. Alig L., Edenhofer A., Hadváry P., Hürzeler M., Knopp D., Müller M., Steiner B., Trzeciak A., Weller T. Low molecular weight, non-peptide fibrinogen receptor antagonists. J Med Chem. 1992 Nov 13;35(23):4393–4407. doi: 10.1021/jm00101a017. [DOI] [PubMed] [Google Scholar]
  2. Aoki Y., Kim Y. T., Stillwell R., Kim T. J., Pillai S. The SH2 domains of Src family kinases associate with Syk. J Biol Chem. 1995 Jun 30;270(26):15658–15663. doi: 10.1074/jbc.270.26.15658. [DOI] [PubMed] [Google Scholar]
  3. Asselin J., Gibbins J. M., Achison M., Lee Y. H., Morton L. F., Farndale R. W., Barnes M. J., Watson S. P. A collagen-like peptide stimulates tyrosine phosphorylation of syk and phospholipase C gamma2 in platelets independent of the integrin alpha2beta1. Blood. 1997 Feb 15;89(4):1235–1242. [PubMed] [Google Scholar]
  4. Bauer J. S., Schreiner C. L., Giancotti F. G., Ruoslahti E., Juliano R. L. Motility of fibronectin receptor-deficient cells on fibronectin and vitronectin: collaborative interactions among integrins. J Cell Biol. 1992 Jan;116(2):477–487. doi: 10.1083/jcb.116.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Briesewitz R., Kern A., Smilenov L. B., David F. S., Marcantonio E. E. The membrane-cytoplasm interface of integrin alpha subunits is critical for receptor latency. Mol Biol Cell. 1996 Oct;7(10):1499–1509. doi: 10.1091/mbc.7.10.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown P. J., Juliano R. L. Monoclonal antibodies to distinctive epitopes on the alpha and beta subunits of the fibronectin receptor. Exp Cell Res. 1988 Aug;177(2):303–318. doi: 10.1016/0014-4827(88)90464-8. [DOI] [PubMed] [Google Scholar]
  7. Bu J. Y., Shaw A. S., Chan A. C. Analysis of the interaction of ZAP-70 and syk protein-tyrosine kinases with the T-cell antigen receptor by plasmon resonance. Proc Natl Acad Sci U S A. 1995 May 23;92(11):5106–5110. doi: 10.1073/pnas.92.11.5106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cambier J. C. Antigen and Fc receptor signaling. The awesome power of the immunoreceptor tyrosine-based activation motif (ITAM). J Immunol. 1995 Oct 1;155(7):3281–3285. [PubMed] [Google Scholar]
  9. Cary L. A., Chang J. F., Guan J. L. Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn. J Cell Sci. 1996 Jul;109(Pt 7):1787–1794. doi: 10.1242/jcs.109.7.1787. [DOI] [PubMed] [Google Scholar]
  10. Chacko G. W., Brandt J. T., Coggeshall K. M., Anderson C. L. Phosphoinositide 3-kinase and p72syk noncovalently associate with the low affinity Fc gamma receptor on human platelets through an immunoreceptor tyrosine-based activation motif. Reconstitution with synthetic phosphopeptides. J Biol Chem. 1996 May 3;271(18):10775–10781. doi: 10.1074/jbc.271.18.10775. [DOI] [PubMed] [Google Scholar]
  11. Chacko G. W., Duchemin A. M., Coggeshall K. M., Osborne J. M., Brandt J. T., Anderson C. L. Clustering of the platelet Fc gamma receptor induces noncovalent association with the tyrosine kinase p72syk. J Biol Chem. 1994 Dec 23;269(51):32435–32440. [PubMed] [Google Scholar]
  12. Chan A. C., Iwashima M., Turck C. W., Weiss A. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Cell. 1992 Nov 13;71(4):649–662. doi: 10.1016/0092-8674(92)90598-7. [DOI] [PubMed] [Google Scholar]
  13. Chen T., Repetto B., Chizzonite R., Pullar C., Burghardt C., Dharm E., Zhao Z., Carroll R., Nunes P., Basu M. Interaction of phosphorylated FcepsilonRIgamma immunoglobulin receptor tyrosine activation motif-based peptides with dual and single SH2 domains of p72syk. Assessment of binding parameters and real time binding kinetics. J Biol Chem. 1996 Oct 11;271(41):25308–25315. doi: 10.1074/jbc.271.41.25308. [DOI] [PubMed] [Google Scholar]
  14. Chen Y. P., O'Toole T. E., Shipley T., Forsyth J., LaFlamme S. E., Yamada K. M., Shattil S. J., Ginsberg M. H. "Inside-out" signal transduction inhibited by isolated integrin cytoplasmic domains. J Biol Chem. 1994 Jul 15;269(28):18307–18310. [PubMed] [Google Scholar]
  15. Chen Y. P., O'Toole T. E., Ylänne J., Rosa J. P., Ginsberg M. H. A point mutation in the integrin beta 3 cytoplasmic domain (S752-->P) impairs bidirectional signaling through alpha IIb beta 3 (platelet glycoprotein IIb-IIIa). Blood. 1994 Sep 15;84(6):1857–1865. [PubMed] [Google Scholar]
  16. Cheng A. M., Rowley B., Pao W., Hayday A., Bolen J. B., Pawson T. Syk tyrosine kinase required for mouse viability and B-cell development. Nature. 1995 Nov 16;378(6554):303–306. doi: 10.1038/378303a0. [DOI] [PubMed] [Google Scholar]
  17. Chu D. H., Spits H., Peyron J. F., Rowley R. B., Bolen J. B., Weiss A. The Syk protein tyrosine kinase can function independently of CD45 or Lck in T cell antigen receptor signaling. EMBO J. 1996 Nov 15;15(22):6251–6261. [PMC free article] [PubMed] [Google Scholar]
  18. Clark E. A., Brugge J. S. Integrins and signal transduction pathways: the road taken. Science. 1995 Apr 14;268(5208):233–239. doi: 10.1126/science.7716514. [DOI] [PubMed] [Google Scholar]
  19. Clark E. A., Brugge J. S. Redistribution of activated pp60c-src to integrin-dependent cytoskeletal complexes in thrombin-stimulated platelets. Mol Cell Biol. 1993 Mar;13(3):1863–1871. doi: 10.1128/mcb.13.3.1863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Clark E. A., Shattil S. J., Ginsberg M. H., Bolen J., Brugge J. S. Regulation of the protein tyrosine kinase pp72syk by platelet agonists and the integrin alpha IIb beta 3. J Biol Chem. 1994 Nov 18;269(46):28859–28864. [PubMed] [Google Scholar]
  21. Costello P. S., Turner M., Walters A. E., Cunningham C. N., Bauer P. H., Downward J., Tybulewicz V. L. Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells. Oncogene. 1996 Dec 19;13(12):2595–2605. [PubMed] [Google Scholar]
  22. Couture C., Deckert M., Williams S., Russo F. O., Altman A., Mustelin T. Identification of the site in the Syk protein tyrosine kinase that binds the SH2 domain of Lck. J Biol Chem. 1996 Sep 27;271(39):24294–24299. doi: 10.1074/jbc.271.39.24294. [DOI] [PubMed] [Google Scholar]
  23. Cox D., Chang P., Kurosaki T., Greenberg S. Syk tyrosine kinase is required for immunoreceptor tyrosine activation motif-dependent actin assembly. J Biol Chem. 1996 Jul 12;271(28):16597–16602. doi: 10.1074/jbc.271.28.16597. [DOI] [PubMed] [Google Scholar]
  24. Crowley M. T., Harmer S. L., DeFranco A. L. Activation-induced association of a 145-kDa tyrosine-phosphorylated protein with Shc and Syk in B lymphocytes and macrophages. J Biol Chem. 1996 Jan 12;271(2):1145–1152. doi: 10.1074/jbc.271.2.1145. [DOI] [PubMed] [Google Scholar]
  25. Daëron M. Fc receptor biology. Annu Rev Immunol. 1997;15:203–234. doi: 10.1146/annurev.immunol.15.1.203. [DOI] [PubMed] [Google Scholar]
  26. Dedhar S., Hannigan G. E. Integrin cytoplasmic interactions and bidirectional transmembrane signalling. Curr Opin Cell Biol. 1996 Oct;8(5):657–669. doi: 10.1016/s0955-0674(96)80107-4. [DOI] [PubMed] [Google Scholar]
  27. El-Hillal O., Kurosaki T., Yamamura H., Kinet J. P., Scharenberg A. M. syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction. Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1919–1924. doi: 10.1073/pnas.94.5.1919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Engvall E., Ruoslahti E. Binding of soluble form of fibroblast surface protein, fibronectin, to collagen. Int J Cancer. 1977 Jul 15;20(1):1–5. doi: 10.1002/ijc.2910200102. [DOI] [PubMed] [Google Scholar]
  29. Ezumi Y., Takayama H., Okuma M. Differential regulation of protein-tyrosine phosphatases by integrin alpha IIb beta 3 through cytoskeletal reorganization and tyrosine phosphorylation in human platelets. J Biol Chem. 1995 May 19;270(20):11927–11934. doi: 10.1074/jbc.270.20.11927. [DOI] [PubMed] [Google Scholar]
  30. Fox J. E., Lipfert L., Clark E. A., Reynolds C. C., Austin C. D., Brugge J. S. On the role of the platelet membrane skeleton in mediating signal transduction. Association of GP IIb-IIIa, pp60c-src, pp62c-yes, and the p21ras GTPase-activating protein with the membrane skeleton. J Biol Chem. 1993 Dec 5;268(34):25973–25984. [PubMed] [Google Scholar]
  31. Frangioni J. V., Oda A., Smith M., Salzman E. W., Neel B. G. Calpain-catalyzed cleavage and subcellular relocation of protein phosphotyrosine phosphatase 1B (PTP-1B) in human platelets. EMBO J. 1993 Dec;12(12):4843–4856. doi: 10.1002/j.1460-2075.1993.tb06174.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Frelinger A. L., 3rd, Du X. P., Plow E. F., Ginsberg M. H. Monoclonal antibodies to ligand-occupied conformers of integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) alter receptor affinity, specificity, and function. J Biol Chem. 1991 Sep 15;266(26):17106–17111. [PubMed] [Google Scholar]
  33. Gibbins J., Asselin J., Farndale R., Barnes M., Law C. L., Watson S. P. Tyrosine phosphorylation of the Fc receptor gamma-chain in collagen-stimulated platelets. J Biol Chem. 1996 Jul 26;271(30):18095–18099. doi: 10.1074/jbc.271.30.18095. [DOI] [PubMed] [Google Scholar]
  34. Grondin P., Plantavid M., Sultan C., Breton M., Mauco G., Chap H. Interaction of pp60c-src, phospholipase C, inositol-lipid, and diacyglycerol kinases with the cytoskeletons of thrombin-stimulated platelets. J Biol Chem. 1991 Aug 25;266(24):15705–15709. [PubMed] [Google Scholar]
  35. Guan J. L., Chen H. C. Signal transduction in cell-matrix interactions. Int Rev Cytol. 1996;168:81–121. [PubMed] [Google Scholar]
  36. Haas T. A., Plow E. F. The cytoplasmic domain of alphaIIb beta3. A ternary complex of the integrin alpha and beta subunits and a divalent cation. J Biol Chem. 1996 Mar 15;271(11):6017–6026. doi: 10.1074/jbc.271.11.6017. [DOI] [PubMed] [Google Scholar]
  37. Haimovich B., Lipfert L., Brugge J. S., Shattil S. J. Tyrosine phosphorylation and cytoskeletal reorganization in platelets are triggered by interaction of integrin receptors with their immobilized ligands. J Biol Chem. 1993 Jul 25;268(21):15868–15877. [PubMed] [Google Scholar]
  38. Hamawy M. M., Mergenhagen S. E., Siraganian R. P. Cell adherence to fibronectin and the aggregation of the high affinity immunoglobulin E receptor synergistically regulate tyrosine phosphorylation of 105-115-kDa proteins. J Biol Chem. 1993 Mar 5;268(7):5227–5233. [PubMed] [Google Scholar]
  39. Huang M. M., Bolen J. B., Barnwell J. W., Shattil S. J., Brugge J. S. Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7844–7848. doi: 10.1073/pnas.88.17.7844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Huang M. M., Lipfert L., Cunningham M., Brugge J. S., Ginsberg M. H., Shattil S. J. Adhesive ligand binding to integrin alpha IIb beta 3 stimulates tyrosine phosphorylation of novel protein substrates before phosphorylation of pp125FAK. J Cell Biol. 1993 Jul;122(2):473–483. doi: 10.1083/jcb.122.2.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Hughes P. E., Renshaw M. W., Pfaff M., Forsyth J., Keivens V. M., Schwartz M. A., Ginsberg M. H. Suppression of integrin activation: a novel function of a Ras/Raf-initiated MAP kinase pathway. Cell. 1997 Feb 21;88(4):521–530. doi: 10.1016/s0092-8674(00)81892-9. [DOI] [PubMed] [Google Scholar]
  42. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  43. Ichinohe T., Takayama H., Ezumi Y., Arai M., Yamamoto N., Takahashi H., Okuma M. Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI. J Biol Chem. 1997 Jan 3;272(1):63–68. doi: 10.1074/jbc.272.1.63. [DOI] [PubMed] [Google Scholar]
  44. Jabril-Cuenod B., Zhang C., Scharenberg A. M., Paolini R., Numerof R., Beaven M. A., Kinet J. P. Syk-dependent phosphorylation of Shc. A potential link between FcepsilonRI and the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2. J Biol Chem. 1996 Jul 5;271(27):16268–16272. doi: 10.1074/jbc.271.27.16268. [DOI] [PubMed] [Google Scholar]
  45. Juliano R. Cooperation between soluble factors and integrin-mediated cell anchorage in the control of cell growth and differentiation. Bioessays. 1996 Nov;18(11):911–917. doi: 10.1002/bies.950181110. [DOI] [PubMed] [Google Scholar]
  46. Kaplan K. B., Swedlow J. R., Morgan D. O., Varmus H. E. c-Src enhances the spreading of src-/- fibroblasts on fibronectin by a kinase-independent mechanism. Genes Dev. 1995 Jun 15;9(12):1505–1517. doi: 10.1101/gad.9.12.1505. [DOI] [PubMed] [Google Scholar]
  47. Keely P. J., Parise L. V. The alpha2beta1 integrin is a necessary co-receptor for collagen-induced activation of Syk and the subsequent phosphorylation of phospholipase Cgamma2 in platelets. J Biol Chem. 1996 Oct 25;271(43):26668–26676. [PubMed] [Google Scholar]
  48. Kimura T., Sakamoto H., Appella E., Siraganian R. P. Conformational changes induced in the protein tyrosine kinase p72syk by tyrosine phosphorylation or by binding of phosphorylated immunoreceptor tyrosine-based activation motif peptides. Mol Cell Biol. 1996 Apr;16(4):1471–1478. doi: 10.1128/mcb.16.4.1471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Kolanus W., Romeo C., Seed B. T cell activation by clustered tyrosine kinases. Cell. 1993 Jul 16;74(1):171–183. doi: 10.1016/0092-8674(93)90304-9. [DOI] [PubMed] [Google Scholar]
  50. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Kurosaki T., Johnson S. A., Pao L., Sada K., Yamamura H., Cambier J. C. Role of the Syk autophosphorylation site and SH2 domains in B cell antigen receptor signaling. J Exp Med. 1995 Dec 1;182(6):1815–1823. doi: 10.1084/jem.182.6.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Kurosaki T., Takata M., Yamanashi Y., Inazu T., Taniguchi T., Yamamoto T., Yamamura H. Syk activation by the Src-family tyrosine kinase in the B cell receptor signaling. J Exp Med. 1994 May 1;179(5):1725–1729. doi: 10.1084/jem.179.5.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. LaFlamme S. E., Thomas L. A., Yamada S. S., Yamada K. M. Single subunit chimeric integrins as mimics and inhibitors of endogenous integrin functions in receptor localization, cell spreading and migration, and matrix assembly. J Cell Biol. 1994 Sep;126(5):1287–1298. doi: 10.1083/jcb.126.5.1287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Latour S., Fournel M., Veillette A. Regulation of T-cell antigen receptor signalling by Syk tyrosine protein kinase. Mol Cell Biol. 1997 Aug;17(8):4434–4441. doi: 10.1128/mcb.17.8.4434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Law C. L., Chandran K. A., Sidorenko S. P., Clark E. A. Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk. Mol Cell Biol. 1996 Apr;16(4):1305–1315. doi: 10.1128/mcb.16.4.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Law D. A., Nannizzi-Alaimo L., Phillips D. R. Outside-in integrin signal transduction. Alpha IIb beta 3-(GP IIb IIIa) tyrosine phosphorylation induced by platelet aggregation. J Biol Chem. 1996 May 3;271(18):10811–10815. doi: 10.1074/jbc.271.18.10811. [DOI] [PubMed] [Google Scholar]
  57. Leong L., Hughes P. E., Schwartz M. A., Ginsberg M. H., Shattil S. J. Integrin signaling: roles for the cytoplasmic tails of alpha IIb beta 3 in the tyrosine phosphorylation of pp125FAK. J Cell Sci. 1995 Dec;108(Pt 12):3817–3825. doi: 10.1242/jcs.108.12.3817. [DOI] [PubMed] [Google Scholar]
  58. Lin T. H., Rosales C., Mondal K., Bolen J. B., Haskill S., Juliano R. L. Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells. A possible signaling role for the Syk tyrosine kinase. J Biol Chem. 1995 Jul 7;270(27):16189–16197. doi: 10.1074/jbc.270.27.16189. [DOI] [PubMed] [Google Scholar]
  59. Lukashev M. E., Sheppard D., Pytela R. Disruption of integrin function and induction of tyrosine phosphorylation by the autonomously expressed beta 1 integrin cytoplasmic domain. J Biol Chem. 1994 Jul 15;269(28):18311–18314. [PubMed] [Google Scholar]
  60. Maruyama S., Kurosaki T., Sada K., Yamanashi Y., Yamamoto T., Yamamura H. Physical and functional association of cortactin with Syk in human leukemic cell line K562. J Biol Chem. 1996 Mar 22;271(12):6631–6635. doi: 10.1074/jbc.271.12.6631. [DOI] [PubMed] [Google Scholar]
  61. Minoguchi K., Benhamou M., Swaim W. D., Kawakami Y., Kawakami T., Siraganian R. P. Activation of protein tyrosine kinase p72syk by Fc epsilon RI aggregation in rat basophilic leukemia cells. p72syk is a minor component but the major protein tyrosine kinase of pp72. J Biol Chem. 1994 Jun 17;269(24):16902–16908. [PubMed] [Google Scholar]
  62. Miyamoto S., Akiyama S. K., Yamada K. M. Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Science. 1995 Feb 10;267(5199):883–885. doi: 10.1126/science.7846531. [DOI] [PubMed] [Google Scholar]
  63. Miyamoto S., Teramoto H., Gutkind J. S., Yamada K. M. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors. J Cell Biol. 1996 Dec;135(6 Pt 1):1633–1642. doi: 10.1083/jcb.135.6.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Muir T. W., Williams M. J., Ginsberg M. H., Kent S. B. Design and chemical synthesis of a neoprotein structural model for the cytoplasmic domain of a multisubunit cell-surface receptor: integrin alpha IIb beta 3 (platelet GPIIb-IIIa). Biochemistry. 1994 Jun 21;33(24):7701–7708. doi: 10.1021/bi00190a025. [DOI] [PubMed] [Google Scholar]
  65. Müller B., Cooper L., Terhorst C. Molecular cloning of the human homologue to the pig protein-tyrosine kinase syk. Immunogenetics. 1994;39(5):359–362. doi: 10.1007/BF00189234. [DOI] [PubMed] [Google Scholar]
  66. Ota Y., Beitz L. O., Scharenberg A. M., Donovan J. A., Kinet J. P., Samelson L. E. Characterization of Cbl tyrosine phosphorylation and a Cbl-Syk complex in RBL-2H3 cells. J Exp Med. 1996 Nov 1;184(5):1713–1723. doi: 10.1084/jem.184.5.1713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Ozaki Y., Satoh K., Kuroda K., Qi R., Yatomi Y., Yanagi S., Sada K., Yamamura H., Yanabu M., Nomura S. Anti-CD9 monoclonal antibody activates p72syk in human platelets. J Biol Chem. 1995 Jun 23;270(25):15119–15124. doi: 10.1074/jbc.270.25.15119. [DOI] [PubMed] [Google Scholar]
  68. Panchamoorthy G., Fukazawa T., Miyake S., Soltoff S., Reedquist K., Druker B., Shoelson S., Cantley L., Band H. p120cbl is a major substrate of tyrosine phosphorylation upon B cell antigen receptor stimulation and interacts in vivo with Fyn and Syk tyrosine kinases, Grb2 and Shc adaptors, and the p85 subunit of phosphatidylinositol 3-kinase. J Biol Chem. 1996 Feb 9;271(6):3187–3194. doi: 10.1074/jbc.271.6.3187. [DOI] [PubMed] [Google Scholar]
  69. Poole A., Gibbins J. M., Turner M., van Vugt M. J., van de Winkel J. G., Saito T., Tybulewicz V. L., Watson S. P. The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO J. 1997 May 1;16(9):2333–2341. doi: 10.1093/emboj/16.9.2333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Qian D., Weiss A. T cell antigen receptor signal transduction. Curr Opin Cell Biol. 1997 Apr;9(2):205–212. doi: 10.1016/s0955-0674(97)80064-6. [DOI] [PubMed] [Google Scholar]
  71. Qin S., Minami Y., Hibi M., Kurosaki T., Yamamura H. Syk-dependent and -independent signaling cascades in B cells elicited by osmotic and oxidative stress. J Biol Chem. 1997 Jan 24;272(4):2098–2103. doi: 10.1074/jbc.272.4.2098. [DOI] [PubMed] [Google Scholar]
  72. Rabinowich H., Manciulea M., Herberman R. B., Whiteside T. L. Beta1 integrin-mediated activation of focal adhesion kinase and its association with Fyn and Zap-70 in human NK cells. J Immunol. 1996 Nov 1;157(9):3860–3868. [PubMed] [Google Scholar]
  73. Reth M., Wienands J. Initiation and processing of signals from the B cell antigen receptor. Annu Rev Immunol. 1997;15:453–479. doi: 10.1146/annurev.immunol.15.1.453. [DOI] [PubMed] [Google Scholar]
  74. Rodríguez-Fernández J. L., Rozengurt E. Bombesin, bradykinin, vasopressin, and phorbol esters rapidly and transiently activate Src family tyrosine kinases in Swiss 3T3 cells. Dissociation from tyrosine phosphorylation of p125 focal adhesion kinase. J Biol Chem. 1996 Nov 1;271(44):27895–27901. doi: 10.1074/jbc.271.44.27895. [DOI] [PubMed] [Google Scholar]
  75. Rowley R. B., Burkhardt A. L., Chao H. G., Matsueda G. R., Bolen J. B. Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation. J Biol Chem. 1995 May 12;270(19):11590–11594. doi: 10.1074/jbc.270.19.11590. [DOI] [PubMed] [Google Scholar]
  76. Sastry S. K., Horwitz A. F. Adhesion-growth factor interactions during differentiation: an integrated biological response. Dev Biol. 1996 Dec 15;180(2):455–467. doi: 10.1006/dbio.1996.0319. [DOI] [PubMed] [Google Scholar]
  77. Sastry S. K., Horwitz A. F. Integrin cytoplasmic domains: mediators of cytoskeletal linkages and extra- and intracellular initiated transmembrane signaling. Curr Opin Cell Biol. 1993 Oct;5(5):819–831. doi: 10.1016/0955-0674(93)90031-k. [DOI] [PubMed] [Google Scholar]
  78. Scarborough R. M., Naughton M. A., Teng W., Rose J. W., Phillips D. R., Nannizzi L., Arfsten A., Campbell A. M., Charo I. F. Design of potent and specific integrin antagonists. Peptide antagonists with high specificity for glycoprotein IIb-IIIa. J Biol Chem. 1993 Jan 15;268(2):1066–1073. [PubMed] [Google Scholar]
  79. Schaller M. D., Borgman C. A., Cobb B. S., Vines R. R., Reynolds A. B., Parsons J. T. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192–5196. doi: 10.1073/pnas.89.11.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Schaller M. D., Otey C. A., Hildebrand J. D., Parsons J. T. Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains. J Cell Biol. 1995 Sep;130(5):1181–1187. doi: 10.1083/jcb.130.5.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Scharenberg A. M., Lin S., Cuenod B., Yamamura H., Kinet J. P. Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering. EMBO J. 1995 Jul 17;14(14):3385–3394. doi: 10.1002/j.1460-2075.1995.tb07344.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Schlaepfer D. D., Hunter T. Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src. J Biol Chem. 1997 May 16;272(20):13189–13195. doi: 10.1074/jbc.272.20.13189. [DOI] [PubMed] [Google Scholar]
  83. Schwartz M. A., Schaller M. D., Ginsberg M. H. Integrins: emerging paradigms of signal transduction. Annu Rev Cell Dev Biol. 1995;11:549–599. doi: 10.1146/annurev.cb.11.110195.003001. [DOI] [PubMed] [Google Scholar]
  84. Shattil S. J., Haimovich B., Cunningham M., Lipfert L., Parsons J. T., Ginsberg M. H., Brugge J. S. Tyrosine phosphorylation of pp125FAK in platelets requires coordinated signaling through integrin and agonist receptors. J Biol Chem. 1994 May 20;269(20):14738–14745. [PubMed] [Google Scholar]
  85. Shiue L., Green J., Green O. M., Karas J. L., Morgenstern J. P., Ram M. K., Taylor M. K., Zoller M. J., Zydowsky L. D., Bolen J. B. Interaction of p72syk with the gamma and beta subunits of the high-affinity receptor for immunoglobulin E, Fc epsilon RI. Mol Cell Biol. 1995 Jan;15(1):272–281. doi: 10.1128/mcb.15.1.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Shiue L., Zoller M. J., Brugge J. S. Syk is activated by phosphotyrosine-containing peptides representing the tyrosine-based activation motifs of the high affinity receptor for IgE. J Biol Chem. 1995 May 5;270(18):10498–10502. doi: 10.1074/jbc.270.18.10498. [DOI] [PubMed] [Google Scholar]
  87. Takata M., Kurosaki T. The catalytic activity of Src-family tyrosine kinase is required for B cell antigen receptor signaling. FEBS Lett. 1995 Nov 6;374(3):407–411. doi: 10.1016/0014-5793(95)01160-g. [DOI] [PubMed] [Google Scholar]
  88. Taylor J. A., Karas J. L., Ram M. K., Green O. M., Seidel-Dugan C. Activation of the high-affinity immunoglobulin E receptor Fc epsilon RI in RBL-2H3 cells is inhibited by Syk SH2 domains. Mol Cell Biol. 1995 Aug;15(8):4149–4157. doi: 10.1128/mcb.15.8.4149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Teramoto H., Salem P., Robbins K. C., Bustelo X. R., Gutkind J. S. Tyrosine phosphorylation of the vav proto-oncogene product links FcepsilonRI to the Rac1-JNK pathway. J Biol Chem. 1997 Apr 18;272(16):10751–10755. doi: 10.1074/jbc.272.16.10751. [DOI] [PubMed] [Google Scholar]
  90. Turner M., Mee P. J., Costello P. S., Williams O., Price A. A., Duddy L. P., Furlong M. T., Geahlen R. L., Tybulewicz V. L. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature. 1995 Nov 16;378(6554):298–302. doi: 10.1038/378298a0. [DOI] [PubMed] [Google Scholar]
  91. Williams S., Couture C., Gilman J., Jascur T., Deckert M., Altman A., Mustelin T. Reconstitution of T cell antigen receptor-induced Erk2 kinase activation in Lck-negative JCaM1 cells by Syk. Eur J Biochem. 1997 Apr 1;245(1):84–90. doi: 10.1111/j.1432-1033.1997.00084.x. [DOI] [PubMed] [Google Scholar]
  92. Yamada K. M., Geiger B. Molecular interactions in cell adhesion complexes. Curr Opin Cell Biol. 1997 Feb;9(1):76–85. doi: 10.1016/s0955-0674(97)80155-x. [DOI] [PubMed] [Google Scholar]
  93. Yan S. R., Huang M., Berton G. Signaling by adhesion in human neutrophils: activation of the p72syk tyrosine kinase and formation of protein complexes containing p72syk and Src family kinases in neutrophils spreading over fibrinogen. J Immunol. 1997 Feb 15;158(4):1902–1910. [PubMed] [Google Scholar]
  94. Yanabu M., Ozaki Y., Nomura S., Miyake T., Miyazaki Y., Kagawa H., Yamanaka Y., Asazuma N., Satoh K., Kume S. Tyrosine phosphorylation and p72syk activation by an anti-glycoprotein Ib monoclonal antibody. Blood. 1997 Mar 1;89(5):1590–1598. [PubMed] [Google Scholar]
  95. Yanagi S., Sada K., Tohyama Y., Tsubokawa M., Nagai K., Yonezawa K., Yamamura H. Translocation, activation and association of protein-tyrosine kinase (p72syk) with phosphatidylinositol 3-kinase are early events during platelet activation. Eur J Biochem. 1994 Sep 1;224(2):329–333. doi: 10.1111/j.1432-1033.1994.00329.x. [DOI] [PubMed] [Google Scholar]
  96. Ylänne J., Chen Y., O'Toole T. E., Loftus J. C., Takada Y., Ginsberg M. H. Distinct functions of integrin alpha and beta subunit cytoplasmic domains in cell spreading and formation of focal adhesions. J Cell Biol. 1993 Jul;122(1):223–233. doi: 10.1083/jcb.122.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Zoller K. E., MacNeil I. A., Brugge J. S. Protein tyrosine kinases Syk and ZAP-70 display distinct requirements for Src family kinases in immune response receptor signal transduction. J Immunol. 1997 Feb 15;158(4):1650–1659. [PubMed] [Google Scholar]

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