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Thromb Haemost 1993; 70(01): 224-228
DOI: 10.1055/s-0038-1646195
State-of-the-Art Lecture
Platelet Signaling
Schattauer GmbH Stuttgart

Regulation of Platelet Anchorage and Signaling by Integrin αIIbβ3

Sanford J Shattil
Hematology-Oncology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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Publication History

Publication Date:
03 July 2018 (online)

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  • References

  • 1 Roth GJ. Platelets and blood vessels: The adhesion event. Immunol Today 1992; 13: 100-105
    CrossrefPubMedGoogle Scholar
  • 2 Poncz M, Eisman R, Heidenreich R, et al. Structure of the platelet membrane glycoprotein lib. Homology to the alpha subunits of the vitronectin and fibronectin membrane receptors. J Biol Chem 1987; 262: 8476-8482
    PubMedGoogle Scholar
  • 3 Gulino D, Boudignon C, Zhang L, Concord E, Rabiet MJ, Mar-guerie G. Ca2+-binding properties of the platelet glycoprotein IIb lig-and-interacting domain. J Biol Chem 1992; 267: 1001-1007
    PubMedGoogle Scholar
  • 4 Fitzgerald LA, Steiner B, Rail Jr SC, Lo SS, Phillips DR. Protein sequence of endothelial glycoprotein IIIa derived from a cDNA clone. Identity with platelet glycoprotein IIIa and similarity to “integrin”. I Biol Chem 1987; 262: 3936-3939
    PubMedGoogle Scholar
  • 5 Beer J, Coller BS. Evidence that platelet glycoprotein IIIa has a large disulfide-bonded loop that is susceptible to proteolytic cleavage. J Biol Chem 1989; 264: 17564-17573
    PubMedGoogle Scholar
  • 6 Calvete IJ, Henschen A, González-Rodríguez J. Assignment of disulphide bonds in human platelet GPIIIa. A disulphide pattern for the β-subunits of the integrin family. Biochem J 1991; 274: 63-71
    CrossrefPubMedGoogle Scholar
  • 7 Weisel JW, Nagaswami C, Vilaire G, Bennett JS. Examination of the platelet membrane glycoprotein IIb-IIIa complex and its interaction with fibrinogen and other ligands by electron microscopy. J Biol Chem 1992; 267: 16637-16643
    PubMedGoogle Scholar
  • 8 Plow EF, D'Souza SE, Ginsberg MH. Ligand binding to GP Ilb-IIIa: A status report. Sem Thromb Hemostas 1992; 18: 324-332
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Lam SC, Plow EF, Smith MA. et al.: Evidence that arginyl-glycyl-aspartate peptides and fibrinogen gamma chain peptides share a common binding site on platelets. J Biol Chem 1987; 262: 947-950
    PubMedGoogle Scholar
  • 10 Bennett JS, Shattil SJ, Power JW, Gartner TK. Interaction of fibrinogen with its platelet receptor. Differential aspects of alpha and gamma chain fibrinogen peptides on the glycoprotein Ilb-IIIa complex. J Biol Chem 1988; 263: 12948-12953
    PubMedGoogle Scholar
  • 11 Rao SN. Bioactive conformation of Arg-Gly-Asp by X-ray data analyses and molecular mechanics. Peptide Res 1992; 5: 148-155
    PubMedGoogle Scholar
  • 12 Adler M, Lazarus RA, Dennis MS, Wagner G. Solution structure of kistrin, a potent platelet aggregation inhibitor and GP Ilb-IIIa antagonist. Science 1991; 253: 445-448
    CrossrefPubMedGoogle Scholar
  • 13 Blumenstein M, Matsueda GR, Timmons S, Hawiger J. A β-turn is present in the 392-411 segment of the human fibrinogen gamma-chain. Effects of structural changes in this segment on affinity to antibody 4A5. Biochemistry 1992; 31: 1069240698
    PubMedGoogle Scholar
  • 14 Kirschbaum NE, Mosesson MW, Amrani DL. Characterization of the gamma chain platelet binding site on fibrinogen fragment D. Blood 1992; 79: 2643-2648
    PubMedGoogle Scholar
  • 15 Farrell DH, Thiagarajan P, Chung DW, Davie EW. Role of fibrinogen α and γ chain sites in platelet aggregation. Proc Natl Acad Sci USA 1992; 89: 10729-10732
    CrossrefPubMedGoogle Scholar
  • 16 Loftus JC, O'Toole TE, Plow EF, Glass A, Frelinger AL, Ginsberg MH. A β3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation. Science 1990; 249: 915-918
    CrossrefPubMedGoogle Scholar
  • 17 Bajt ML, Ginsberg MH, Frelinger III AL, Berndt MC, Loftus JC. A spontaneous mutation of integrin αnbβ3 (platelet glycoprotein Ilb-IIIa) helps define a ligand binding site. J Biol Chem 1992; 267: 3789-3794
    PubMedGoogle Scholar
  • 18 Weiss HJ, Turitto VT, Baumgartner HR. Further evidence that glycoprotein Ilb-IIIa mediates platelet spreading on subendothelium. Thromb Haemostas 1991; 65: 202-205
    PubMedGoogle Scholar
  • 19 Frojmovic MM, O'Toole TE, Plow EF, Loftus JC, Ginsberg MH. Platelet glycoprotein IIb-IIIa (αIIbβ3 integrin) confers fibrinogen-and activation-dependent aggregation on heterologous cells. Blood 1991; 78: 369-376
    PubMedGoogle Scholar
  • 20 Leung LLK. Role of thrombospondin in platelet aggregation. J Clin Invest 1984; 74: 1764-1777
    CrossrefPubMedGoogle Scholar
  • 21 Frelinger III AL, Du X, Plow EF, Ginsberg MH. Monoclonal antibodies to ligand-occupied conformers of integrin αIIbβ3 (glycoprotein Ilb-IIIa) alter receptor affinity, specificity, and function. J Biol Chem 1991; 266: 17106-17111
    PubMedGoogle Scholar
  • 22 Zamarron C, Ginsberg MH, Plow EF. Monoclonal antibodies specific for a conformationally altered state of fibrinogen. Thromb Haemostas 1990; 64: 41-46
    PubMedGoogle Scholar
  • 23 Peerschke EIB. Events occurring after thrombin-induced fibrinogen binding to platelets. Sem Thromb Hemostas 1992; 18: 34-43
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Savage B, Shattil SJ, Ruggeri ZM. Modulation of platelet function through adhesion receptors. A dual role for glycoprotein Ilb-IIIa (integrin αIIbβ3) mediated by fibrinogen and glycoprotein Ib-von Willebrand factor. J Biol Chem 1992; 267: 11300-11306
    PubMedGoogle Scholar
  • 25 Nachmias VT, Golla R. Vinculin in relation to stress fibers in spread platelets. Cell Motil Cytoskel 1991; 20: 190-202
    CrossrefPubMedGoogle Scholar
  • 26 Brass LF, Manning DR, Shattil SJ. GTP-binding proteins and platelet activation. In: Progress in Hemostasis and Thrombosis. 10th ed. Coller BS. (ed). W.B. Saunders Co.; Philadelphia: 1991. pp. 127-174
    Google Scholar
  • 27 Shattil SJ, Hoxie JA, Cunningham M, Brass LF. Changes in the platelet membrane glycoprotein IIb-IIIa complex during platelet activation. J Biol Chem 1985; 260: 11107-11114
    PubMedGoogle Scholar
  • 28 Sims PJ, Ginsberg MH, Plow EF, Shattil SJ. Effect of platelet activation on the conformation of the plasma membrane glycoprotein Ilb-IIIa complex. J Biol Chem 1991; 266: 7345-7352
    PubMedGoogle Scholar
  • 29 Simon MI, Strathmann MP, Gautam N. Diversity of G proteins in signal transduction. Science 1991; 252: 802-808
    CrossrefPubMedGoogle Scholar
  • 30 Shattil SJ, Brass LF. Induction of the fibrinogen receptor on human platelets by intracellular mediators. J Biol Chem 1987; 262: 992-1000
    PubMedGoogle Scholar
  • 31 Shattil SJ, Cunningham M, Wiedmer T, Zhao J, Sims PJ, Brass LF. Regulation of glycoprotein IIb-IIIa receptor function studied with platelets permeabilized by the pore-forming complement proteins C5b-9. J Biol Chem 1992; 267: 18424-18431
    PubMedGoogle Scholar
  • 32 Hillery CA, Smyth SS, Parise LV. Phosphorylation of human platelet glycoprotein IIIa (GPIIIa). Dissociation from fibrinogen receptor activation and phosphorylation of GPIIIa in vitro . J Biol Chem 1991; 266: 14663-14669
    PubMedGoogle Scholar
  • 33 Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990; 61: 203-212
    CrossrefPubMedGoogle Scholar
  • 34 Cantley LC, Auger KR, Carpenter C. et al.: Oncogenes and signal transduction. Cell 1991; 64: 281-302
    CrossrefPubMedGoogle Scholar
  • 35 Shattil SJ, Brugge JS. Protein tyrosine phosphorylation and the adhesive functions of platelets. Current Opin Cell Biol 1991; 3: 869-879
    CrossrefPubMedGoogle Scholar
  • 36 Freeman RM, Plutzky J, Neel BG. Identification of a human src homology 2-containing protein-tyrosine phosphatase: A putative homolog of Drosophila corkscrew. Proc Natl Acad Sci USA 1992; 89: 11239-11243
    CrossrefPubMedGoogle Scholar
  • 37 Gu M, York JD, Warshawsky I, Majerus PW. Identification, cloning, and expression of a cytosolic megakaryocyte protein-tyrosine-phos-phatase with sequence homology to cytoskeletal protein 4.1. Proc Natl Acad Sci USA 1991; 88: 5867-5871
    CrossrefPubMedGoogle Scholar
  • 38 Taniguchi T, Kitagawa H, Yasue S. et al.: Protein-tyrosine kinase p72syk is activated by thrombin and is negatively regulated through Ca2+ mobilization in platelets. J Biol Chem 1993; 268: 2277-2279
    PubMedGoogle Scholar
  • 39 Zhang J, Fry MJ, Waterfield MD. et al.: Activated phosphoinositide 3-kinase associates with membrane skeleton in thrombin-exposed platelets. J Biol Chem 1992; 267: 4686-4692
    PubMedGoogle Scholar
  • 40 Cichowski K, McCormick F, Brugge JS. p21rasGAP association with Fyn, Lyn, and Yes in thrombin-activated platelets. J Biol Chem 1992; 267: 5025-5028
    PubMedGoogle Scholar
  • 41 Torti M, Lapetina EG. The role of raplb and p21ras GTPase-activat-ing protein in the regulation of phospholipase C-γI in human platelets. Proc Natl Acad Sci USA. 1992 (in press)
    PubMedGoogle Scholar
  • 42 Sjölander A, Lapetina EG. Agonist-induced association of the p21rasGTPase-activating protein with phosphatidylinositol 3-kinase. Biochem Biophys Res Commun 1992; 189: 1503-1508
    CrossrefPubMedGoogle Scholar
  • 43 Shattil SJ, Wiedmer T, Sims PJ, Zhao J, Cunningham M, Brass LF. Permeabilization of the platelet plasma membrane for study of the intracellular regulation of GP IIb-IIIa receptor function. Blood 1991; 78: 183a (abstr)
    PubMedGoogle Scholar
  • 44 Pumiglia KM, Lau LF, Huang CK, Burroughs S, Feinstein MB. Activation of signal transduction in platelets by the tyrosine phosphatase inhibitor pervanadate (vanadyl hydroperoxide). Biochem J. 1992 (in press)
    PubMedGoogle Scholar
  • 45 Morii N, Teruuchi T, Tominaga T. et al.: A rho gene product in human blood platelets. II. Effects of the ADP-ribosylation by botu-linum C3 ADP-ribosyltransferase on platelet aggregation. J Biol Chem 1992; 267: 20921-20926
    PubMedGoogle Scholar
  • 46 O'Toole TE, Mandelman D, Forsyth J, Shattil SJ, Plow EF, Ginsberg MH. Modulation of the affinity of integrin αIIbβ3 (GPIIb-IIIa) by the cytoplasmic domain of αIIb . Science 1991; 254: 845-847
    CrossrefPubMedGoogle Scholar
  • 47 Chen Y, Djaffer I, Pidard D. et al.: The absence of activation of platelet GPIIb-IIIa, the integrin, αIIbβ3, is associated with a point mutation of the cytoplasmic domain of GPIIIa (β3) in a variant type of Glanzmann's thrombasthenia. Blood 1991; 78: 279a (abstr)
    PubMedGoogle Scholar
  • 48 Brown E, Hooper L, Ho T, Gresham H. Integrin-associated protein: A 50-kd plasma membrane antigen physically and functionally associated with integrins. J Cell Biol 1990; 111: 2785-2794
    CrossrefPubMedGoogle Scholar
  • 49 Pullman WE, Bodmer WF. Cloning and characterization of a gene that regulates cell adhesion. Nature 1992; 356: 529-532
    CrossrefPubMedGoogle Scholar
  • 50 Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992; 69: 11-25
    CrossrefPubMedGoogle Scholar
  • 51 Juliano RL, Haskill S. Signal transduction from the extracellular matrix. J Cell Biol 1993; 120: 577-585
    CrossrefPubMedGoogle Scholar
  • 52 Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB, Parsons JT. PP125FAK, a structurally unique protein tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci USA 1992; 89: 5192-5196
    CrossrefPubMedGoogle Scholar
  • 53 Guan JL, Shalloway D. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature 1992; 358: 690-692
    CrossrefPubMedGoogle Scholar
  • 54 Burridge K, Turner CE, Romer LH. Tyrosine phosphorylation of paxillin and ppl25FAK accompanies cell adhesion to extracellular matrix: A role in cytoskeletal assembly. J Cell Biol 1992; 119: 893-903
    CrossrefPubMedGoogle Scholar
  • 55 Huang MM, Lipfert L, Ginsberg MH, Plow EF, Brugge JS, Shattil SJ. Binding of multivalent ligands to integrin GP Ilb-IIIa stimulates tyrosine phosphorylation of a restricted set of platelet proteins. Blood 1992; 80: 165a (abstr)
    PubMedGoogle Scholar
  • 56 Haimovich B, Brugge JS, Cunningham M, et al. Bidirectional flow of information across the platelet fibrinogen receptor. Clin Res 1992; 40: 349A (abstr)
    PubMedGoogle Scholar