Integrin αIIbβ3 outside-in signaling

Blood

Volumn 130, Issue 14, 2017, Pages 1607-1619

  Durrant, Tom N ^a   Van Den Bosch, Marion T ^a,b   Hers, Ingeborg ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b BRITISH COLUMBIA CANCER AGENCY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ADAP PROTEIN; ADAPTOR PROTEIN; ALPHA INTEGRIN; BETA3 INTEGRIN; CALCIUM AND INTEGRIN BINDING PROTEIN 1; FOCAL ADHESION KINASE; INTEGRIN ALPHA 2B BETA 3; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOLIPASE C GAMMA2; PROTEIN KINASE C; PROTEIN KINASE SYK; PROTEIN TYROSINE KINASE; RHO FACTOR; SLP 76 PROTEIN; UNCLASSIFIED DRUG; FIBRINOGEN RECEPTOR;

ENZYME ACTIVATION; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; THROMBOCYTE FUNCTION; ANIMAL; HEMOSTASIS; METABOLISM; PATHOPHYSIOLOGY; THROMBOCYTE; THROMBOSIS;

ANIMALS; BLOOD PLATELETS; HEMOSTASIS; HUMANS; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; SIGNAL TRANSDUCTION; THROMBOSIS;

EID: 85030720129     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2017-03-773614     Document Type: Review

References (165)

1. Qin J, Vinogradova O, Plow EF. Integrin bidirectional signaling: a molecular view. PLoS Biol. 2004;2(6):e169.
2. Hynes RO. Integrins: a family of cell surface receptors. Cell. 1987;48(4):549-554.
3. Hynes RO. The emergence of integrins: a personal and historical perspective. Matrix Biol. 2004;23(6):333-340.
4. Parise LV, Phillips DR. Reconstitution of the purified platelet fibrinogen receptor. Fibrinogen binding properties of the glycoprotein IIb-IIIa complex. J Biol Chem. 1985;260(19): 10698-10707.
5. Jennings LK, Phillips DR. Purification of glycoproteins IIb and III from human platelet plasma membranes and characterization of a calcium-dependent glycoprotein IIb-III complex. J Biol Chem. 1982;257(17):10458-10466.
6. Bennett JS, Berger BW, Billings PC. The structure and function of platelet integrins. J Thromb Haemost. 2009;7(suppl 1):200-205.
7. Campbell ID, Humphries MJ. Integrin structure, activation, and interactions. Cold Spring Harb Perspect Biol. 2011;3(3):a004994.
8. Shattil SJ, Newman PJ. Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood. 2004;104(6):1606-1615.
9. Plow EF, D’Souza SE, Ginsberg MH. Ligand binding to GPIIb-IIIa: a status report. Semin Thromb Hemost. 1992;18(3):324-332.
10. Shattil SJ. The beta3 integrin cytoplasmic tail: protein scaffold and control freak. J Thromb Haemost. 2009;7(suppl 1):210-213.
11. Maxwell MJ, Yuan Y, Anderson KE, Hibbs ML, Salem HH, Jackson SP. SHIP1 and Lyn kinase negatively regulate integrin alpha IIb beta 3 signaling in platelets. J Biol Chem. 2004;279(31): 32196-32204.
12. Koivisto L, Heino J, Häkkinen L, Larjava H. Integrins in wound healing. Adv Wound Care. 2014;3(12):762-783.
13. Lagarrigue F, Kim C, Ginsberg MH. The Rap1-RIAM-talin axis of integrin activation and blood cell function. Blood. 2016;128(4):479-487.
14. Ye F, Kim C, Ginsberg MH. Molecular mechanism of inside-out integrin regulation. J Thromb Haemost. 2011;9(suppl 1):20-25.
15. Ginsberg MH. Integrin activation. BMB Rep. 2014;47(12):655-659.
16. Ye F, Snider AK, Ginsberg MH. Talin and kindlin: the one-two punch in integrin activation. Front Med. 2014;8(1):6-16.
17. Shattil SJ, Kim C, Ginsberg MH. The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol. 2010;11(4):288-300.
18. Coller BS, Shattil SJ. The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood. 2008;112(8):3011-3025.
19. Wagner CL, Mascelli MA, Neblock DS, Weisman HF, Coller BS, Jordan RE. Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to human platelets. Blood. 1996;88(3):907-914.
20. 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(5):599-611.
21. Hughes PE, Diaz-Gonzalez F, Leong L, et al. Breaking the integrin hinge. A defined structural constraint regulates integrin signaling. J Biol Chem. 1996;271(12):6571-6574.
22. Goggs R, Poole AW. Platelet signaling: a primer. J Vet Emerg Crit Care. 2012;22(1):5-29.
23. Li Z, Delaney MK, O’Brien KA, Du X. Signaling during platelet adhesion and activation. Arterioscler Thromb Vasc Biol. 2010;30(12): 2341-2349.
24. Humphries JD, Byron A, Humphries MJ. Integrin ligands at a glance. J Cell Sci. 2006;119(Pt 19): 3901-3903.
25. Farrell DH, Thiagarajan P, Chung DW, Davie EW. Role of fibrinogen alpha and gamma chain sites in platelet aggregation. Proc Natl Acad Sci USA. 1992;89(22):10729-10732.
26. Bennett JS. Structure and function of the platelet integrin alphaIIbbeta3. J Clin Invest. 2005; 115(12):3363-3369.
27. Litvinov RI, Farrell DH, Weisel JW, Bennett JS. The platelet integrin aIIbb3 differentially interacts with fibrin versus fibrinogen. J Biol Chem. 2016; 291(15):7858-7867.
28. Ley K, Rivera-Nieves J, Sandborn WJ, Shattil S. Integrin-based therapeutics: biological basis, clinical use and new drugs. Nat Rev Drug Discov. 2016;15(3):173-183.
29. Tohyama Y, Tohyama K, Tsubokawa M, Asahi M, Yoshida Y, Yamamura H. Outside-in signaling of soluble and solid-phase fibrinogen through integrin alphaIIbbeta3 is different and cooperative with each other in a megakaryoblastic leukemia cell line, CMK. Blood. 1998;92(4):1277-1286.
30. Jirousková M, Jaiswal JK, Coller BS. Ligand density dramatically affects integrin alpha IIb beta 3-mediated platelet signaling and spreading. Blood. 2007;109(12):5260-5269.
31. Fong KP, Zhu H, Span LM, et al. Directly activating the integrin aIIbb3 initiates outside-in signaling by causing aIIbb3 clustering. J Biol Chem. 2016;291(22):11706-11716.
32. Legate KR, Wickström SA, Fässler R. Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev. 2009;23(4):397-418.
33. Buensuceso C, de Virgilio M, Shattil SJ. Detection of integrin alpha IIbbeta 3 clustering in living cells. J Biol Chem. 2003;278(17): 15217-15224.
34. Li R, Mitra N, Gratkowski H, et al. Activation of integrin alphaIIbbeta3 by modulation of transmembrane helix associations. Science. 2003;300(5620):795-798.
35. Hato T, Pampori N, Shattil SJ. Complementary roles for receptor clustering and conformational change in the adhesive and signaling functions of integrin alphaIIb beta3. J Cell Biol. 1998; 141(7):1685-1695.
36. Phillips DR, Agin PP. Platelet membrane defects in Glanzmann’s thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest. 1977;60(3):535-545.
37. Chen YP, O’Toole TE, Ylänne J, Rosa JP, Ginsberg MH. 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;84(6): 1857-1865.
38. Bury L, Malara A, Gresele P, Balduini A. Outside-in signalling generated by a constitutively activated integrin aIIbb3 impairs proplatelet formation in human megakaryocytes. PLoS One. 2012;7(4):e34449.
39. Bosch X, Marrugat J, Sanchis J. Platelet glycoprotein IIb/IIIa blockers during percutaneous coronary intervention and as the initial medical treatment of non-ST segment elevation acute coronary syndromes. Cochrane Database Syst Rev. 2013; (11):CD002130.
40. Nathan S, Rao SV. Radial versus femoral access for percutaneous coronary intervention: implications for vascular complications and bleeding. Curr Cardiol Rep. 2012;14(4):502-509.
41. Brasselet C, Tassan S, Nazeyrollas P, Hamon M, Metz D. Randomised comparison of femoral versus radial approach for percutaneous coronary intervention using abciximab in acute myocardial infarction: results of the FARMI trial. Heart. 2007;93(12):1556-1561.
42. Tsakiris DA, Scudder L, Hodivala-Dilke K, Hynes RO, Coller BS. Hemostasis in the mouse (Mus musculus): a review. Thromb Haemost. 1999; 81(2):177-188.
43. Shen B, Zhao X, O’Brien KA, et al. A directional switch of integrin signalling and a new antithrombotic strategy. Nature. 2013;503(7474): 131-135.
44. Watson SP, Auger JM, McCarty OJ, Pearce AC. GPVI and integrin alphaIIb beta3 signaling in platelets. J Thromb Haemost. 2005;3(8): 1752-1762.
45. Guidetti GF, Canobbio I, Torti M. PI3K/Akt in platelet integrin signaling and implications in thrombosis. Adv Biol Regul. 2015;59:36-52.
46. Watanabe N, Bodin L, Pandey M, et al. Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin alphaIIbbeta3. J Cell Biol. 2008;181(7): 1211-1222.
47. Battram AM, Durrant TN, Agbani EO, et al. The phosphatidylinositol 3,4,5-trisphosphate (PI (3,4,5)P3)-binder Rasa3 regulates phosphoinositide 3-kinase (PI3K)-dependent integrin aIIbb3 outside-in signaling. J Biol Chem. 2017;292(5):1691-1704.
48. Kasirer-Friede A, Moran B, Nagrampa-Orje J, et al. ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other agonists. Blood. 2007;109(3):1018-1025.
49. O’Toole TE, Loftus JC, Du XP, et al. Affinity modulation of the alpha IIb beta 3 integrin (platelet GPIIb-IIIa) is an intrinsic property of the receptor. Cell Regul. 1990;1(12):883-893.
50. Plow EF, Qin J. The role of RIAM in platelets put to a test. Blood. 2015;125(2):207-208.
51. Haling JR, Monkley SJ, Critchley DR, Petrich BG. Talin-dependent integrin activation is required for fibrin clot retraction by platelets. Blood. 2011;117(5):1719-1722.
52. Kasirer-Friede A, Ruggeri ZM, Shattil SJ. Role for ADAP in shear flow-induced platelet mechanotransduction. Blood. 2010;115(11): 2274-2282.
53. Huang MM, Lipfert L, Cunningham M, Brugge JS, Ginsberg MH, Shattil SJ. Adhesive ligand binding to integrin alpha IIb beta 3 stimulates tyrosine phosphorylation of novel protein substrates before phosphorylation of pp125FAK. J Cell Biol. 1993;122(2):473-483.
54. Golden A, Brugge JS, Shattil SJ. Role of platelet membrane glycoprotein IIb-IIIa in agonist-induced tyrosine phosphorylation of platelet proteins. J Cell Biol. 1990;111(6 Pt 2): 3117-3127.
55. Obergfell A, Eto K, Mocsai A, 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(2):265-275.
56. Séverin S, Nash CA, Mori J, et al. Distinct and overlapping functional roles of Src family kinases in mouse platelets. J Thromb Haemost. 2012; 10(8):1631-1645.
57. Senis YA, Mazharian A, Mori J. Src family kinases: at the forefront of platelet activation. Blood. 2014;124(13):2013-2024.
58. Burkhart JM, Vaudel M, Gambaryan S, et al. The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways. Blood. 2012;120(15):e73-e82.
59. Rowley JW, Oler AJ, Tolley ND, et al. Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood. 2011;118(14): e101-e111.
60. Kim MS, Pinto SM, Getnet D, et al. A draft map of the human proteome. Nature. 2014; 509(7502):575-581.
61. 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(23):13298-13302.
62. Wu Y, Span LM, Nygren P, et al. The tyrosine kinase c-Src specifically binds to the active integrin aIIbb3 to initiate outside-in signaling in platelets. J Biol Chem. 2015;290(25): 15825-15834.
63. Gong H, Shen B, Flevaris P, et al. G protein subunit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin “outside-in” signaling. Science. 2010;327(5963):340-343.
64. Senis YA, Tomlinson MG, Ellison S, et al. The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis. Blood. 2009;113(20):4942-4954.
65. Ablooglu AJ, Kang J, Petrich BG, Ginsberg MH, Shattil SJ. Antithrombotic effects of targeting alphaIIbbeta3 signaling in platelets. Blood. 2009; 113(15):3585-3592.
66. Gao J, Zoller KE, Ginsberg MH, Brugge JS, Shattil SJ. Regulation of the pp72syk protein tyrosine kinase by platelet integrin alpha IIb beta 3. EMBO J. 1997;16(21):6414-6425.
67. Woodside DG, Obergfell A, Leng L, et al. Activation of Syk protein tyrosine kinase through interaction with integrin beta cytoplasmic domains. Curr Biol. 2001;11(22):1799-1804.
68. Boylan B, Gao C, Rathore V, Gill JC, Newman DK, Newman PJ. Identification of FcgammaRIIa as the ITAM-bearing receptor mediating alphaIIbbeta3 outside-in integrin signaling in human platelets. Blood. 2008;112(7):2780-2786.
69. Law DA, DeGuzman FR, Heiser P, Ministri-Madrid K, Killeen N, Phillips DR. Integrin cytoplasmic tyrosine motif is required for outside-in alphaIIbbeta3 signalling and platelet function. Nature. 1999;401(6755):808-811.
70. Phillips DR, Prasad KS, Manganello J, Bao M, Nannizzi-Alaimo L. Integrin tyrosine phosphorylation in platelet signaling. Curr Opin Cell Biol. 2001;13(5):546-554.
71. Jenkins AL, Nannizzi-Alaimo L, Silver D, et al. Tyrosine phosphorylation of the beta3 cytoplasmic domain mediates integrin-cytoskeletal interactions. J Biol Chem. 1998; 273(22):13878-13885.
72. Law DA, Nannizzi-Alaimo L, Phillips DR. Outside-in integrin signal transduction. Alpha IIb beta 3-(GP IIb IIIa) tyrosine phosphorylation induced by platelet aggregation. J Biol Chem. 1996;271(18):10811-10815.
73. Xi X, Flevaris P, Stojanovic A, et al. Tyrosine phosphorylation of the integrin beta 3 subunit regulates beta 3 cleavage by calpain. J Biol Chem. 2006;281(40):29426-29430.
74. Harburger DS, Calderwood DA. Integrin signalling at a glance. J Cell Sci. 2009;122(Pt 2): 159-163.
75. 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(8):5916-5923.
76. Wonerow P, Pearce AC, Vaux DJ, Watson SP. A critical role for phospholipase Cgamma2 in alphaIIbbeta3-mediated platelet spreading. J Biol Chem. 2003;278(39):37520-37529.
77. Pearce AC, McCarty OJ, Calaminus SD, Vigorito E, Turner M, Watson SP. Vav family proteins are required for optimal regulation of PLCg2 by integrin alpha IIb beta 3. Biochem J. 2007; 401(3):753-761.
78. Buensuceso CS, Obergfell A, Soriani A, et al. Regulation of outside-in signaling in platelets by integrin-associated protein kinase C beta. J Biol Chem. 2005;280(1):644-653.
79. Soriani A, Moran B, de Virgilio M, et al. A role for PKCtheta in outside-in alpha(IIb)beta3 signaling. J Thromb Haemost. 2006;4(3):648-655.
80. van den Bosch MT, Poole AW, Hers I. Cytohesin-2 phosphorylation by protein kinase C relieves the constitutive suppression of platelet dense granule secretion by ADP-ribosylation factor 6. J Thromb Haemost. 2014;12(5): 726-735.
81. Lipfert L, Haimovich B, Schaller MD, Cobb BS, Parsons JT, Brugge JS. Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets. J Cell Biol. 1992;119(4):905-912.
82. Hitchcock IS, Fox NE, Prévost N, Sear K, Shattil SJ, Kaushansky K. Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage specific FAK knockout. Blood. 2008;111(2): 596-604.
83. Tadokoro S, Nakazawa T, Kamae T, et al. A potential role for a-actinin in inside-out aIIbb3 signaling. Blood. 2011;117(1):250-258.
84. Judd BA, Myung PS, Leng L, et al. Hematopoietic reconstitution of SLP-76 corrects hemostasis and platelet signaling through alpha IIb beta 3 and collagen receptors. Proc Natl Acad Sci USA. 2000;97(22):12056-12061.
85. Clements JL, Lee JR, Gross B, et al. Fetal hemorrhage and platelet dysfunction in SLP-76deficient mice. J Clin Invest. 1999;103(1):19-25.
86. Leisner TM, Freeman TC, Black JL, Parise LV. CIB1: a small protein with big ambitions. FASEB J. 2016;30(8):2640-2650.
87. Naik UP, Naik MU. Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen. Blood. 2003; 102(4):1355-1362.
88. Naik UP, Patel PM, Parise LV. Identification of a novel calcium-binding protein that interacts with the integrin alphaIIb cytoplasmic domain. J Biol Chem. 1997;272(8):4651-4654.
89. Yuan W, Leisner TM, McFadden AW, et al. CIB1 is an endogenous inhibitor of agonist-induced integrin alphaIIbbeta3 activation. J Cell Biol. 2006;172(2):169-175.
90. Naik MU, Naik TU, Summer R, Naik UP. Binding of CIB1 to the aIIb tail of aIIbb3 is required for FAK recruitment and activation in platelets. PLoS One. 2017;12(5):e0176602.
91. Martin V, Guillermet-Guibert J, Chicanne G, et al. Deletion of the p110beta isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo. Blood. 2010; 115(10):2008-2013.
92. Canobbio I, Stefanini L, Cipolla L, et al. Genetic evidence for a predominant role of PI3Kbeta catalytic activity in ITAM- and integrin-mediated signaling in platelets. Blood. 2009;114(10): 2193-2196.
93. Jackson SP, Schoenwaelder SM, Goncalves I, et al. PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med. 2005;11(5): 507-514.
94. Laurent PA, Severin S, Gratacap MP, Payrastre B. Class I PI 3-kinases signaling in platelet activation and thrombosis: PDK1/Akt/GSK3 axis and impact of PTEN and SHIP1. Adv Biol Regul. 2014;54:162-174.
95. Laurent PA, Séverin S, Hechler B, Vanhaesebroeck B, Payrastre B, Gratacap MP. Platelet PI3Kb and GSK3 regulate thrombus stability at a high shear rate. Blood. 2015;125(5): 881-888.
96. Saci A, Rendu F, Bachelot-Loza C. Platelet alpha IIb-beta 3 integrin engagement induces the tyrosine phosphorylation of Cbl and its association with phosphoinositide 3-kinase and Syk. Biochem J. 2000;351(Pt 3):669-676.
97. Cipolla L, Consonni A, Guidetti G, et al. The proline-rich tyrosine kinase Pyk2 regulates platelet integrin aIIbb3 outside-in signaling. J Thromb Haemost. 2013;11(2):345-356.
98. Buitrago L, Langdon WY, Sanjay A, Kunapuli SP. Tyrosine phosphorylated c-Cbl regulates platelet functional responses mediated by outside-in signaling. Blood. 2011;118(20): 5631-5640.
99. Durrant TN, Hutchinson JL, Heesom KJ, et al. In-depth PtdIns(3,4,5)P-3 signalosome analysis identifies DAPP1 as a negative regulator of GPVI-driven platelet function. Blood Adv. 2017; 1(14):918-932.
100. O’Brien KA, Gartner TK, Hay N, Du X. ADP-stimulated activation of Akt during integrin outside-in signaling promotes platelet spreading by inhibiting glycogen synthase kinase-3b. Arterioscler Thromb Vasc Biol. 2012;32(9): 2232-2240.
101. Chen X, Zhang Y, Wang Y, et al. PDK1 regulates platelet activation and arterial thrombosis. Blood. 2013;121(18):3718-3726.
102. Pleines I, Hagedorn I, Gupta S, et al. Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis. Blood. 2012;119(4):1054-1063.
103. Leng L, Kashiwagi H, Ren XD, Shattil SJ. RhoA and the function of platelet integrin alphaIIbbeta3. Blood. 1998;91(11):4206-4215.
104. Shen B, Estevez B, Xu Z, et al. The interaction of Ga13 with integrin b1 mediates cell migration by dynamic regulation of RhoA. Mol Biol Cell. 2015; 26(20):3658-3670.
105. Flevaris P, Stojanovic A, Gong H, Chishti A, Welch E, Du X. A molecular switch that controls cell spreading and retraction. J Cell Biol. 2007; 179(3):553-565.
106. Xiang B, Zhang G, Ye S, et al. Characterization of a novel integrin binding protein, VPS33B, which is important for platelet activation and in vivo thrombosis and hemostasis. Circulation. 2015;132(24):2334-2344.
107. Aslan JE, McCarty OJ. Rho GTPases in platelet function. J Thromb Haemost. 2013;11(1):35-46.
108. Price LS, Leng J, Schwartz MA, Bokoch GM. Activation of Rac and Cdc42 by integrins mediates cell spreading. Mol Biol Cell. 1998; 9(7):1863-1871.
109. McCarty OJ, Larson MK, Auger JM, et al. Rac1 is essential for platelet lamellipodia formation and aggregate stability under flow. J Biol Chem. 2005;280(47):39474-39484.
110. Akbar H, Kim J, Funk K, et al. Genetic and pharmacologic evidence that Rac1 GTPase is involved in regulation of platelet secretion and aggregation. J Thromb Haemost. 2007;5(8): 1747-1755.
111. Pleines I, Elvers M, Strehl A, et al. Rac1 is essential for phospholipase C-gamma2 activation in platelets. Pflugers Arch. 2009; 457(5):1173-1185.
112. Flevaris P, Li Z, Zhang G, Zheng Y, Liu J, Du X. Two distinct roles of mitogen-activated protein kinases in platelets and a novel Rac1-MAPK-dependent integrin outside-in retractile signaling pathway. Blood. 2009;113(4):893-901.
113. Pleines I, Eckly A, Elvers M, et al. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. Blood. 2010;115(16):3364-3373.
114. Akbar H, Shang X, Perveen R, et al. Gene targeting implicates Cdc42 GTPase in GPVI and non-GPVI mediated platelet filopodia formation, secretion and aggregation. PLoS One. 2011; 6(7):e22117.
115. Kashiwagi H, Shiraga M, Kato H, et al. Expression and subcellular localization of WAVE isoforms in the megakaryocyte/platelet lineage. J Thromb Haemost. 2005;3(2):361-368.
116. Pleines I, Dütting S, Cherpokova D, et al. Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42. Blood. 2013;122(18): 3178-3187.
117. Shcherbina A, Cooley J, Lutskiy MI, Benarafa C, Gilbert GE, Remold-O’Donnell E. WASP plays a novel role in regulating platelet responses dependent on alphaIIbbeta3 integrin outside-in signalling. Br J Haematol. 2010;148(3):416-427.
118. Calaminus SD, McCarty OJ, Auger JM, et al. A major role for Scar/WAVE-1 downstream of GPVI in platelets. J Thromb Haemost. 2007;5(3): 535-541.
119. Li Z, Kim ES, Bearer EL. Arp2/3 complex is required for actin polymerization during platelet shape change. Blood. 2002;99(12):4466-4474.
120. Morse EM, Brahme NN, Calderwood DA. Integrin cytoplasmic tail interactions. Biochemistry. 2014;53(5):810-820.
121. Horton ER, Byron A, Askari JA, et al. Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly. Nat Cell Biol. 2015;17(12): 1577-1587.
122. Zaidel-Bar R, Itzkovitz S, Ma’ayan A, Iyengar R, Geiger B. Functional atlas of the integrin adhesome. Nat Cell Biol. 2007;9(8):858-867.
123. Petrich BG, Marchese P, Ruggeri ZM, et al. Talin is required for integrin-mediated platelet function in hemostasis and thrombosis. J Exp Med. 2007; 204(13):3103-3111.
124. Poulter NS, Pollitt AY, Davies A, et al. Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich syndrome protein and ARP2/3 complex. Nat Commun. 2015;6: 7254.
125. Nieswandt B, Moser M, Pleines I, et al. Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo. J Exp Med. 2007;204(13): 3113-3118.
126. Petrich BG, Fogelstrand P, Partridge AW, et al. The antithrombotic potential of selective blockade of talin-dependent integrin alpha IIb beta 3 (platelet GPIIb-IIIa) activation. J Clin Invest. 2007;117(8):2250-2259.
127. Mitsios JV, Prevost N, Kasirer-Friede A, et al. What is vinculin needed for in platelets? J Thromb Haemost. 2010;8(10):2294-2304.
128. Zeiler M, Moser M, Mann M. Copy number analysis of the murine platelet proteome spanning the complete abundance range. Mol Cell Proteomics. 2014;13(12):3435-3445.
129. Roca-Cusachs P, del Rio A, Puklin-Faucher E, Gauthier NC, Biais N, Sheetz MP. Integrin-dependent force transmission to the extracellular matrix by a-actinin triggers adhesion maturation. Proc Natl Acad Sci USA. 2013;110(15): E1361-E1370.
130. Lin SY, Raval S, Zhang Z, et al. The protein-tyrosine phosphatase SHP-1 regulates the phosphorylation of alpha-actinin. J Biol Chem. 2004;279(24):25755-25764.
131. Sakata A, Ohmori T, Nishimura S, et al. Paxillin is an intrinsic negative regulator of platelet activation in mice. Thromb J. 2014;12(1):1.
132. Chen X, Fan X, Tan J, et al. Palladin is involved in platelet activation and arterial thrombosis. Thromb Res. 2017;149:1-8.
133. Moser M, Nieswandt B, Ussar S, Pozgajova M, Fässler R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med. 2008;14(3):325-330.
134. Honda S, Shirotani-Ikejima H, Tadokoro S, Tomiyama Y, Miyata T. The integrin-linked kinase-PINCH-parvin complex supports integrin aIIbb3 activation. PLoS One. 2013;8(12): e85498.
135. Tucker KL, Sage T, Stevens JM, et al. A dual role for integrin-linked kinase in platelets: regulating integrin function and alpha-granule secretion. Blood. 2008;112(12):4523-4531.
136. Jones CI, Tucker KL, Sasikumar P, et al. Integrin-linked kinase regulates the rate of platelet activation and is essential for the formation of stable thrombi. J Thromb Haemost. 2014;12(8):1342-1352.
137. Takizawa H, Nishimura S, Takayama N, et al. Lnk regulates integrin alphaIIbbeta3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo. J Clin Invest. 2010;120(1):179-190.
138. Niki M, Nayak MK, Jin H, et al. Dok-1 negatively regulates platelet integrin aIIbb3 outside-in signalling and inhibits thrombosis in mice. Thromb Haemost. 2016;115(5):969-978.
139. Hughan SC, Spring CM, Schoenwaelder SM, et al. Dok-2 adaptor protein regulates the shear-dependent adhesive function of platelet integrin aIIbb3 in mice. J Biol Chem. 2014;289(8): 5051-5060.
140. Moscardó A, Santos MT, Latorre A, Madrid I, Vallés J. Serine/threonine phosphatases regulate platelet aIIbb3 integrin receptor outside-in signaling mechanisms and clot retraction. Life Sci. 2013;93(20):707-713.
141. Dai B, Wu P, Xue F, et al. Integrin-aIIbb3-mediated outside-in signalling activates a negative feedback pathway to suppress platelet activation. Thromb Haemost. 2016;116(5): 918-930.
142. Goschnick MW, Lau LM, Wee JL, et al. Impaired “outside-in” integrin alphaIIbbeta3 signaling and thrombus stability in TSSC6-deficient mice. Blood. 2006;108(6):1911-1918.
143. Lau LM, Wee JL, Wright MD, et al. The tetraspanin superfamily member CD151 regulates outside-in integrin alphaIIbbeta3 signaling and platelet function. Blood. 2004; 104(8):2368-2375.
144. Huang Y, Joshi S, Xiang B, et al. Arf6 controls platelet spreading and clot retraction via integrin aIIbb3 trafficking. Blood. 2016;127(11): 1459-1467.
145. Zou Z, Chen H, Schmaier AA, Hynes RO, Kahn ML. Structure-function analysis reveals discrete beta3 integrin inside-out and outside-in signaling pathways in platelets. Blood. 2007;109(8): 3284-3290.
146. Legate KR, Fässler R. Mechanisms that regulate adaptor binding to beta-integrin cytoplasmic tails. J Cell Sci. 2009;122(Pt 2):187-198.
147. Metcalf DG, Moore DT, Wu Y, et al. NMR analysis of the alphaIIb beta3 cytoplasmic interaction suggests a mechanism for integrin regulation. Proc Natl Acad Sci USA. 2010; 107(52):22481-22486.
148. Kiema T, Lad Y, Jiang P, et al. The molecular basis of filamin binding to integrins and competition with talin. Mol Cell. 2006;21(3): 337-347.
149. Berrou E, Adam F, Lebret M, et al. Gain-of-function mutation in filamin A potentiates platelet integrin aIIbb3 activation. Arterioscler Thromb Vasc Biol. 2017;37(6):1087-1097.
150. Moser M, Legate KR, Zent R, Fässler R. The tail of integrins, talin, and kindlins. Science. 2009; 324(5929):895-899.
151. Calderwood DA, Campbell ID, Critchley DR. Talins and kindlins: partners in integrin-mediated adhesion. Nat Rev Mol Cell Biol. 2013;14(8): 503-517.
152. Zaidel-Bar R, Cohen M, Addadi L, Geiger B. Hierarchical assembly of cell-matrix adhesion complexes. Biochem Soc Trans. 2004;32(Pt3): 416-420.
153. 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(3): 305-311.
154. Feng S, Lu X, Reséndiz JC, Kroll MH. Pathological shear stress directly regulates platelet alphaIIbbeta3 signaling. Am J Physiol Cell Physiol. 2006;291(6):C1346-C1354.
155. Naik MU, Nigam A, Manrai P, et al. CIB1 deficiency results in impaired thrombosis: the potential role of CIB1 in outside-in signaling through integrin alpha IIb beta 3. J Thromb Haemost. 2009;7(11):1906-1914.
156. Tsai HJ, Huang CL, Chang YW, et al. Disabled-2 is required for efficient hemostasis and platelet activation by thrombin in mice. Arterioscler Thromb Vasc Biol. 2014;34(11):2404-2412.
157. Moers A, Nieswandt B, Massberg S, et al. G13 is an essential mediator of platelet activation in hemostasis and thrombosis. Nat Med. 2003; 9(11):1418-1422.
158. Wee JL, Jackson DE. The Ig-ITIM superfamily member PECAM-1 regulates the “outside-in” signaling properties of integrin alpha(IIb)beta3 in platelets. Blood. 2005;106(12):3816-3823.
159. Hall KJ, Harper MT, Gilio K, Cosemans JM, Heemskerk JW, Poole AW. Genetic analysis of the role of protein kinase Ctheta in platelet function and thrombus formation. PLoS One. 2008;3(9):e3277.
160. Konopatskaya O, Gilio K, Harper MT, et al. PKCalpha regulates platelet granule secretion and thrombus formation in mice. J Clin Invest. 2009;119(2):399-407.
161. Canobbio I, Cipolla L, Consonni A, et al. Impaired thrombin-induced platelet activation and thrombus formation in mice lacking the Ca (21)-dependent tyrosine kinase Pyk2. Blood. 2013;121(4):648-657.
162. Sladojevic N, Oh GT, Kim HH, et al. Decreased thromboembolic stroke but not atherosclerosis or vascular remodeling in mice with ROCK2-deficient platelets [published online ahead of print 14 April 2017]. Cardiovasc Res. doi: 10.1093/cvr/cvx071.
163. Naik MU, Stalker TJ, Brass LF, Naik UP. JAM-A protects from thrombosis by suppressing integrin aIIbb3-dependent outside-in signaling in platelets. Blood. 2012;119(14):3352-3360.
164. Séverin S, Gratacap MP, Lenain N, et al. Deficiency of Src homology 2 domain-containing inositol 5-phosphatase 1 affects platelet responses and thrombus growth. J Clin Invest. 2007;117(4):944-952.
165. Uchtmann K, Park ER, Bergsma A, Segula J, Edick MJ, Miranti CK. Homozygous loss of mouse tetraspanin CD82 enhances integrin aIIbb3 expression and clot retraction in platelets. Exp Cell Res. 2015;339(2):261-269.