RGT, a synthetic peptide corresponding to the integrin ß3 cytoplasmic C-terminal sequence, selectively inhibits outside-in signaling in human platelets by disrupting the interaction of integrin αIIbβ3 with Src kinase

Blood

Volumn 112, Issue 3, 2008, Pages 592-602

  Su, Xiaoyu ^a   Mi, Jianqing ^a   Yan, Jinsong ^a   Flevaris, Panagiotis ^b   Lu, Yuanjing ^a   Liu, Hongchen ^a   Ruan, Zheng ^a   Wang, Xuefeng ^a   Kieffer, Nelly ^a   Chen, Saijuan ^a   Du, Xiaoping ^b   Xi, Aodong ^a  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE DIPHOSPHATE; BETA3 INTEGRIN; FIBRINOGEN; FIBRINOGEN RECEPTOR; PADGEM PROTEIN; PROTEIN TYROSINE KINASE; RISTOCETIN; SYNTHETIC PEPTIDE; THROMBIN; PEPTIDE FRAGMENT;

ARTICLE; BLOOD CLOT RETRACTION; CARBOXY TERMINAL SEQUENCE; CONTROLLED STUDY; CYTOPLASM; FIBRIN CLOT; HUMAN; HUMAN CELL; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PHOSPHORYLATION; THROMBOCYTE; THROMBOCYTE ADHESION; THROMBOCYTE AGGREGATION; THROMBOCYTE RELEASE REACTION; DOSE RESPONSE; DRUG EFFECT; METABOLISM; PHOSPHORYLATION; PROTEIN BINDING; SIGNAL TRANSDUCTION; SYNTHESIS; THROMBOCYTE ADHESIVENESS;

CLOT RETRACTION; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INTEGRIN BETA3; PEPTIDE FRAGMENTS; PHOSPHORYLATION; PLATELET ADHESIVENESS; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PROTEIN BINDING; SIGNAL TRANSDUCTION; SRC-FAMILY KINASES;

EID: 50949109753     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2007-09-110437     Document Type: Article

References (51)

1. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110:673-687.
2. Ginsberg MH, Partridge A, Shattil SJ. Integrin regulation. Curr Opin Cell Biol. 2005;17:509-516.
3. Tadokoro S, Shattil SJ, Eto K, et al. Talin binding to integrin β tails: a final common step in integrin activation. Science. 2003;302:103-106.
4. Vinogradova O, Velyvis A, Velyviene A, et al. A structural mechanism of integrin αIIbβ3 "insideout" activation as regulated by its cytoplasmic face. Cell. 2002;110:587-597.
5. Shattil SJ, Kashiwagi H, Pampori N. Integrin signaling: the platelet paradigm. Blood. 1998;91:2645-2657.
6. Law DA, DeGuzman FR, Heiser P, et al. Integrin cytoplasmic tyrosine motif is required for outside-in alphaIIbbeta3 signalling and platelet function. Nature. 1999;401:808-811.
7. Obergfell A, Eto K, Mocsai A, et al. Coordinate interactions of Csk, Src, and Syk kinases with αIIbβ3 initiate integrin signaling to the cytoskeleton. J Cell Biol. 2002;157:265-275.
8. Arias-Salgado EG, Lizano S, Shattil SJ, Ginsberg MH. Specification of the direction of adhesive signaling by the integrin β cytoplasmic domain. J Biol Chem. 2005;280:29699-29707.
9. Flevaris P, Stojanovic A, Gong H, et al. A molecular switch that controls cell spreading and retraction. J Cell Biol. 2007;179:553-565.
10. Xi X, Bodnar RJ, Li Z, Lam SC, Du X. Critical roles for the COOH-terminal NITY and RGT sequences of the integrin β3 cytoplasmic domain in inside-out and outside-in signaling. J Cell Biol. 2003;162:329-339.
11. Xi X, Flevaris P, Stojanovic A, et al. Tyrosine phosphorylation of the integrin β3 subunit regulates β3 cleavage by calpain. J Biol Chem. 2006; 281:29426-29430.
12. Lau LM, Wee JL, Wright MD, et al. The tetraspanin superfamily member CD151 regulates outside-in integrin αIIbβ3 signaling and platelet function. Blood. 2004;104:2368-2375.
13. Nanda N, Andre P, Bao M, et al. Platelet aggregation induces platelet aggregate stability via SLAM family receptor signaling. Blood. 2005;106:3028-3034.
14. Pozgajova M, Sachs UJ, Hein L, Nieswandt B. Reduced thrombus stability in mice lacking the α2A-adrenergic receptor. Blood. 2006;108:510-514.
15. Andre P, Prasad KS, Denis CV, et al. CD40L stabilizes arterial thrombi by a β3 integrin-dependent mechanism. Nat Med. 2002;8:247-252.
16. Angelillo-Scherrer A, de Frutos PG, Aparicio C, et al. Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med. 2001;7:215-221.
17. Arias-Salgado EG, Haj F, Dubois C, et al. PTP-1B is an essential positive regulator of platelet integrin signaling. J Cell Biol. 2005;170:837-845.
18. Maxwell MJ, Yuan Y, Anderson KE, et al. SHIP1 and Lyn kinase negatively regulate integrin αIIbβ3 signaling in platelets. J Biol Chem. 2004; 279:32196-32204.
19. Goschnick MW, Lau LM, Wee JL, et al. Impaired "outside-in" integrin αIIbβ3 signaling and thrombus stability in TSSC6-deficient mice. Blood. 2006;108:1911-1918.
20. Wee JL, Jackson DE. The Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signaling properties of integrin αIIbβ3 in platelets. Blood. 2005;106:3816-3823.
21. Tsuboi S. Calcium integrin-binding protein activates platelet integrin αIIbβ3. J Biol Chem. 2002; 277:1919-1923.
22. Li Z, Xi X, Du X. A mitogen-activated protein kinase-dependent signaling pathway in the activation of platelet integrin αIIbβ3. J Biol Chem. 2001; 276:42226-42232.
23. Martin K, Meade G, Moran N, Shields DC, Kenny D. A palmitylated peptide derived from the glycoprotein Ibβ cytoplasmic tail inhibits platelet activation. J Thromb Haemost. 2003;1:2643-2652.
24. Liu XY, Timmons S, Lin YZ, Hawiger J. Identification of a functionally important sequence in the cytoplasmic tail of integrin β3 by using cell-permeable peptide analogs. Proc Natl Acad Sci U S A. 1996;93:11819-11824.
25. Osdoit S, Rosa JP. Fibrin clot retraction by human platelets correlates with αIIbβ3 integrin-dependent protein tyrosine dephosphorylation. J Biol Chem. 2001;276:6703-6710.
26. Podolnikova NP, Yakubenko VP, Volkov GL, Plow EF, Ugarova TP. Identification of a novel binding site for platelet integrins αIIbβ3 (GPIIbIIIa) and α5β1 in the gamma C-domain of fibrinogen. J Biol Chem. 2003;278:32251-32258.
27. Merten M, Thiagarajan P. Role for sulfatides in platelet aggregation. Circulation. 2001;104:2955-2960.
28. Angelillo-Scherrer A, Burnier L, Flores N, et al. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest. 2005;115:237-246.
29. Prevost N, Woulfe DS, Tognolini M, et al. Signaling by ephrinB1 and Eph kinases in platelets promotes Rap1 activation, platelet adhesion, and aggregation via effector pathways that do not require phosphorylation of ephrinB1. Blood. 2004;103:1348-1355.
30. Li Z, Zhang G, Marjanovic JA, Ruan C, Du X. A platelet secretion pathway mediated by cGMPdependent protein kinase. J Biol Chem. 2004;279:42469-42475.
31. Law DA, Nannizzi-Alaimo L, Phillips DR. Outside-in integrin signal transduction: αIIbβ3-(GP IIb IIIa) tyrosine phosphorylation induced by platelet aggregation. J Biol Chem. 1996;271:10811-10815.
32. Arias-Salgado EG, Lizano S, Sarkar S, et al. Src kinase activation by direct interaction with the integrin β cytoplasmic domain. Proc Natl Acad Sci U S A. 2003;100:13298-13302.
33. Prevost N, Woulfe DS, Jiang H, et al. Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets. Proc Natl Acad Sci U S A. 2005;102:9820-9825.
34. Hughes PE, O'Toole TE, Ylanne J, Shattil SJ, Ginsberg MH. The conserved membrane-proximal region of an integrin cytoplasmic domain specifies ligand binding affinity. J Biol Chem. 1995;270:12411-12417.
35. Patil S, Jedsadayanmata A, Wencel-Drake JD, et al. Identification of a talin-binding site in the integrin β3 subunit distinct from the NPLY regulatory motif of post-ligand binding functions: the talin n-terminal head domain interacts with the membrane-proximal region of the β3 cytoplasmic tail. J Biol Chem. 1999;274:28575-28583.
36. Ylanne J, Huuskonen J, O'Toole TE, et al. Mutation of the cytoplasmic domain of the integrin β3 subunit: differential effects on cell spreading, recruitment to adhesion plaques, endocytosis, and phagocytosis. J Biol Chem. 1995;270:9550-9557.
37. Chen YP, O'Toole TE, Ylanne J, Rosa JP, Ginsberg MH. A point mutation in the integrin β3 cytoplasmic domain (S752→P) impairs bidirectional signaling through αIIbβ3 (platelet glycoprotein IIb-IIIa). Blood. 1994;84:1857-1865.
38. Hers I, Donath J, Litjens PE, van Willigen G, Akkerman JW. Inhibition of platelet integrin αIIbβ3 by peptides that interfere with protein kinases and the β3 tail. Arterioscler Thromb Vasc Biol. 2000;20:1651-1660.
39. Litjens PE, Gorter G, Ylänne J, Akkerman JW, van Willigen G. Involvement of the β3 E749ATSTFTN756 region in stabilizing integrin αIIbβ3-ligand interaction. J Thromb Haemost. 2003;1:2216-2224.
40. Litjens PE, Kroner CI, Akkerman JW, Van WG. Cytoplasmic regions of the β3 subunit of integrin αIIbβ3 involved in platelet adhesion on fibrinogen under flow conditions. J Thromb Haemost. 2003; 1:2014-2021.
41. Dai K, Bodnar R, Berndt MC, Du X. A critical role for 14-3-3ζ protein in regulating the VWF binding function of platelet glycoprotein Ib-IX and its therapeutic implications. Blood. 2005;106:1975-1981.
42. Larkin D, Murphy D, Reilly DF, et al. ICln, a novel integrin αIIbβ3-associated protein, functionally regulates platelet activation. J Biol Chem. 2004; 279:27286-27293.
43. Liu J, Jackson CW, Gruppo RA, Jennings LK, Gartner TK. The β3 subunit of the integrin αIIbβ3 regulates alphaIIb-mediated outside-in signaling. Blood. 2005;105:4345-4352.
44. Vinogradova O, Haas T, Plow EF, Qin J. A structural basis for integrin activation by the cytoplasmic tail of the αIIb-subunit. Proc Natl Acad Sci U S A. 2000;97:1450-1455.
45. Stephens G, O'Luanaigh N, Reilly D, et al. A sequence within the cytoplasmic tail of GpIIb independently activates platelet aggregation and thromboxane synthesis. J Biol Chem. 1998;273:20317-20322.
46. Ginsberg M, Pierschbacher MD, Ruoslahti E, Marguerie G, Plow E. Inhibition of fibronectin binding to platelets by proteolytic fragments and synthetic peptides which support fibroblast adhesion. J Biol Chem. 1985;260:3931-3936.
47. Wang Z, Leisner TM, Parise LV. Platelet α2β1 integrin activation: contribution of ligand internalization and the alpha2-cytoplasmic domain. Blood. 2003;102:1307-1315.
48. Tremuth L, Kreis S, Melchior C, et al. A fluorescence cell biology approach to map the second integrin-binding site of talin to a 130-amino acid sequence within the rod domain. J Biol Chem. 2004;279:22258-22266.
49. Shattil SJ. Integrins and Src: dynamic duo of adhesion signaling. Trends Cell Biol. 2005;15:399-403.
50. Phillips DR, Conley PB, Sinha U, Andre P. Therapeutic approaches in arterial thrombosis. J Thromb Haemost. 2005;3:1577-1589.
51. Bassler N, Loeffler C, Mangin P, et al. A mechanistic model for paradoxical platelet activation by ligand-mimetic αIIbβ3 (GPIIb/IIIa) antagonists. Arterioscler Thromb Vasc Biol. 2007;27:e9-e15.