Distinct Domains of αIIbβ3 Support Different Aspects of Outside-In Signal Transduction and Platelet Activation Induced by LSARLAF, an αIIbβ3 Interacting Peptide

Jerry M. Derrick; Sanford J. Shattil; Mortimer Poncz; Ralph A. Gruppo; Kent T. Gartner

doi:10.1055/s-0037-1616147

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(03): 894-901
DOI: 10.1055/s-0037-1616147

Review Articles

Schattauer GmbH

Distinct Domains of αIIbβ3 Support Different Aspects of Outside-In Signal Transduction and Platelet Activation Induced by LSARLAF, an αIIbβ3 Interacting Peptide

Jerry M. Derrick

¹University of Memphis, Department of Microbiology and Molecular Cell Biology, Memphis, TN

,

Sanford J. Shattil

²Scripps Research Institute, Department of Vascular Biology, LaJolla, CA

,

Mortimer Poncz

³University of Pennsylvania School of Medicine, Departments of Pediatrics and Medicine, Philadelphia, PA

,

Ralph A. Gruppo

⁴Children’s Hospital Medical Center, Division of Hematology/Oncology, Cincinnati, OH, USA

,

Kent T. Gartner

¹University of Memphis, Department of Microbiology and Molecular Cell Biology, Memphis, TN

› Author Affiliations

Abstract

Summary

The peptide LSARLAF causes αIIbβ3-dependent platelet activation exemplified by secretion, aggregation, spreading and adhesion on fibrinogen, and tyrosine phosphorylation. αIIbβ3-dependent outside-in signal transduction induced by LSARLAF was investigated in variant thrombasthenic platelets which lack most of the cytoplasmic domain of the integrin β3 subunit (αIIbβ3 Δ724). These studies revealed that only certain aspects of this αIIbβ3-dependent outside-in signaling were affected by the β3 truncation. Specifically, αIIbβ3 724 supported LSARLAF-induced platelet aggregation, agglutination and secretion, but failed to trigger cytoskeletal reorganization and platelet spreading on fibrinogen, despite the fact that PMA-induced non αIIbβ3 mediated signaling caused spreading of these platelets on fibrinogen. Thus, distinct domains of αIIbβ3 are required to support different aspects of LSARLAF-induced platelet activation. Furthermore, these studies suggest that not all αIIbβ3-dependent platelet responses require an intact β3 cytoplasmic tail.

Keywords

Outside-in signaling - platelet spreading - tyrosine phosphorylation

Full Text

References

References
1 Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb-IIIa complex. Blood 1988; 71: 831-43.
2 Shattil SJ, Ginsberg MH, Brugge JS. Adhesive signaling in platelets. Curr Opin Cell Biol 1991; 6: 695-704.
3 Clark EA, Brugge JS. Integrins and signal transduction pathways: the road taken. Science 1995; 268: 233-9.
4 Shattil SJ, Kashiwagi H, Pampori N. Integrin signaling: the platelet paradigm. Blood 1998; 91: 2645-57.
5 Huang MM, Lipfert L, Cunningham M, Brugge JS, Ginsberg MH, Shattil SJ. Adhesive ligand binding to integrin αIIbβ3 stimulates tyrosine phosphorylation of novel protein substrates before phosphorylation of pp125FAK. J Cell Biol 1993; 122: 473-83.
6 Savage B, Shattil SJ, Ruggeri ZM. Modulation of platelet function through adhesion receptors a dual role for glycoprotein IIb-IIIa (integrin αIIbβ3) mediated by fibrinogen and glycoprotein Ib-von Willebrand factor. J Biol Chem 1992; 267: 11300-6.
7 Haimovich B, Lipfert L, Brugge J, Shattil SJ. Tyrosine phosphorylation and cytoskeletal reorganization in platelets are triggered by interaction of integrin receptors with their immobilized ligands. J Biol Chem 1993; 268: 15868-77.
8 Derrick JM, Loudon RG, Gartner TK. Peptide LSARLAF activates αIIbβ3 on resting platelets and causes resting platelet aggregate formation without shape change. Thromb Res 1998; 89: 31-40.
9 Ferrell JE, Martin GS. Tyrosine-specific phosphorylation is regulated by glycoprotein IIb-IIIa in platelets. Proc Natl Acad Sci USA 1989; 86: 2234-8.
10 Law DA, Nannizzi-Alaimo L, Phillips DR. Outside-in integrin signal transduction. J Biol Chem 1996; 252: 10811-5.
11 Chen YP, Djaffar I, Pidard D, Steiner B, Cieutat AM, Caen JP, Rosa JP. Ser 752kPro mutation in the cytoplasmic domain of integrin b3 subunit and defective activation of platelet integrin αIIbβ3 in a variant of Glanzmann thrombasthenia. Proc Natl Acad Sci USA 1992; 89: 10169-73.
12 Wang R, Shattil SJ, Ambruso DR, Newman PJ. Truncation of the cytoplasmic domain of β3 in a variant form of Glanzmann thrombasthenia abrogates signaling through the integrin αIIbβ3 complex. J Clin Invest 1997; 100: 2393-403.
13 Chen YP, O’Tool TE, Ylanne J, Rosa JP, Ginsberg MH. A point mutation in the integrin β3 cytoplasmic domain (S752kP) impairs bidirectional signaling through αIIbβ3 (platelet glycoprotein IIb-IIIa). Blood 1994; 84: 1857-65.
14 Shattil SJ, Hoxie JA, Cunningham M, Brass LF. Changes in the platelet membrane glycoprotein IIb-IIIa complex during platelet aggregation. J Biol Chem 1985; 20: 11107-14.
15 Derrick JM, Taylor DB, Loudon RG, Gartner TK. The peptide LSARLAF causes platelet secretion and aggregation by directly activating αIIbβ3. Biochem J 1997; 325: 309-13.
16 Basani RB, French DL, Vilaire G, Brown DL, Chen F, Coller BS, Derrick JM, Gartner TK, Bennett JS, Poncz M. A naturally occurring mutation near the amino terminus of αIIb defines a new region involved in ligand binding to αIIbβ3. Blood 2000; 95: 180-7.
17 Newman PJ, Allen RW, Kahn RA, Kunicki TJ. Quantitation of membrane glycoprotein IIIa on intact human platelets using the monoclonal antibody AP-3. Blood 1985; 65: 227-32.
18 Gartner TK, Bennett JS. The tetrapeptide analog of the cell-attachment site of fibronectin inhibits platelet-aggregation and fibrinogen binding to activated platelets. J Biol Chem 1985; 260: 11891-4.
19 Gartner TK, Amrani DL, Derrick JM. Characterization of adhesion of nonexogenously stimulated and resting platelets in normal plasma to fibrinogen and its fragments. Blood Coag Fibrin 1994; 5: 747-54.
20 Gartner TK, Amrani DL, Derrick JM, Kirschbaum NE, Matsueda GR, Taylor DB. Characterization of adhesion of “resting” and stimulated platelets to fibrinogen and its fragments. Thromb Res 1993; 71: 47-60.
21 Leng L, Kashiwagi H, Ren X-D, Shattil S. RhoA and the function of platelet integrin αIIbβ3. Blood 1998; 91: 4206-16.
22 Bennett JS, Shattil SJ, Power JW, Gartner TK. Interaction of fibrinogen with its platelet receptor: Differential effects of α-chain and γ-chain fibrinogen peptides on the glycoprotein IIb-IIIa complex. J Biol Chem 1988; 263: 12948-53.
23 Poncz M, Rifat S, Coller BS, Newman PJ, Shattil S, Parrella T, Fortina P, Bennett JS. Glanzmann thrombasthenia secondary to a Gly 273→ Asp mutation adjacent to the first calcium-binding domain of platelet glycoprotein IIb. J Clin Invest 1994; 93: 172-9.
24 Leong L, Hughes PE, Schwartz MA, Ginsberg MH, Shattil SJ. Integrin signaling: role for the cytoplasmic tails of αIIbβ3 in the tyrosine phosphorylation of pp125FAK. J Cell Sci 1995; 108: 3817-25.
25 Coller BS. Interaction of normal, thrombasthenic, and Bernard-Soulier platelets with immobilized fibrinogen: defective platelet-fibrinogen interactions in thrombasthenia. Blood 1980; 55: 169-78.
26 Kieffer N, Fitzgerald LA, Wolf D, Cheresh DA, Phillips DR. Adhesive properties of the b3 Integrins: comparison of GPIIb/IIIa and the vitronectin receptor individually expressed in human melanoma cells. J Cell Biol 1991; 113: 451-61.
27 Savage B, Ruggeri ZM. Selective recognition of adhesive sites in surface bound fibrinogen by glycoprotein IIb-IIIa on non activated platelets. J Biol Chem 1991; 266: 11227-33.
28 Schoenwaelder SM, Burridge K. Bidirectional signaling between the cyto-skeleton and Integrins. Curr Opin Cell Biol 1999; 1: 274-86.
29 Miranti CK, Leng L, Maschberger P, Brugge JS, Shattil SJ. Identification of a novel integrin signaling pathway involving the kinase Syk and the guanine nucleotide exchange factor Vav1. Curr Biol 1998; 8: 1289-99.
30 Shattil SJ, Haimovich B, Cunningham M, Lipfert L, Parsons JT, Ginsberg MH, Brugge JS. Tyrosine phosphorylation of pp125FAK in platelets requires coordinated signaling through integrin and agonist receptors. J Biol Chem 1994; 269: 14738-45.
31 Glancotti FG, Ruoslahti E. Integrin Signaling. Science 1999; 285: 1028-32.
32 Danilov YN, Juliano RL. Phorbol ester modulation of integrin-mediated cell adhesion: a post receptor event. J Cell Biol 1989; 108: 1925-33.
33 Rosa J-P, Artcanuthurry V, Grelac F, Maclouf J, Caen J, Levy-Toledano S. Reassessment of protein tyrosine phosphorylation in thrombasthenic platelets: evidence that phosphorylation of cortactin and a 64 kD protein is dependent on thrombin activation and integrin αIIbβ3. Blood 1997; 89: 4385-92.