Structure and function of platelet αIIbβ3

Current Opinion in Hematology

Volumn 4, Issue 5, 1997, Pages 317-322

  Naik, Ulhas P ^a   Parise, Leslie V ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL SURFACE RECEPTOR; FIBRINOGEN; FIBRINOGEN RECEPTOR; INTEGRIN; PROTEIN SUBUNIT; THROMBOCYTE RECEPTOR;

PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN EXPRESSION; RECEPTOR BINDING; SHORT SURVEY; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; THROMBOCYTE AGGREGATION;

EID: 0030841469     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/00062752-199704050-00004     Document Type: Short Survey

References (48)

1. Smyth SS, Joneckis CC, Parise LV: Regulation of vascular integrins. Blood 1993, 81:2827-2843.
2. Phillips DR, Charo IF, Parise LV, Fitzgerald LA: The platelet membrane glycoprotein IIb-IIIa complex. Blood 1988, 71:831-843.
3. 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.
4. Vinciguerra C, Khelif A, Alemany M, Morle F, Grenier C, Uzan G, Gulino D, Dechavanna M, Negrier C: A nonsense mutation in the GPIIb heavy chain (Ser 870 stop) impairs platelet GP IIb-IIIa expression. Br J Hematol 1996, 95:399-407.
5. Kahn MJ, Kieber-Emmons T, Vilaire G, Murali R, Mortimer P, Bennett JS: Effect of mutagenesis of GPIIb amino acid 273 on the expression and conformation of the platelet integrin GPIIb IIIa. Biochemistry 1996, 35:14304-14311.
6. 3. Blood 1996, 88:167-173.
7. 3. J Biol Chem 1996, 271:30544-30547. This intriguing study identifies a 6-amino acid sequence of β3 that is required for heterodimer assembly and demonstrates the expression of a soluble "mini-integrin."
8. Kloczcwiak M, Timmons S, Lukas TJ, Hawiger J: Platelet recognition site on human fibrinogen: synthesis and structure-function relationship of peptides corresponding to the carboxyterminal segment of the γ chain. Biochemistry 1984, 23:1767-1774.
9. Ruoslahti E, Pierschbacher M.D: Arg-Gly-Asp: a versatile cell recognition signal. Cell 1986, 44:517-518.
10. 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.
11. 3, integrins. J Biol Chem 1996, 271:10365-10371.
12. Du XP, Plow EF, Frelinger AL 3d, O'Toole TE, Loftus JC, Ginsberg MH: Platelet glycoprotein IIb-IIIa (αIIbβ3 integrin) confers fibrinogen- and activation-dependent aggregation on heterologous cells. Blood 1991, 78:369-376.
13. Sims PJ Ginsberg MH, Plow EF, Shattil SJ: Effect of platelet activation on the conformation of the plasma membrane glycoprotein IIb-IIIa complex. J Biol Chem 1991, 266:7345-7352.
14. IIbβ3. J Biol Chem 1996, 271:2033-2039.
15. Kamata T, Irie A, Tokuhira M, Takada Y: Critical residues of integrin αIIbβ3 (glycoprotein IIb-IIIa) to fibrinogen and ligand-mimetic antibodies (PAC-1, OP-G2, and U-CP3). J Biol Chem 1996, 271:18610-18615.
16. 3 is dependent on a MIDAS-like domain in the β3 subunit J Biol Chem 1996, 271:21978-21984. A comparison between the MIDAS domain and β3 aids in identifying residues in β3 important for ligand binding.
17. Alemany M, Concord E, Garin J, Vinvon M, Giles A, Marguerie G, Gulino D: Sequence 274-368 in the β3-subunit of the integrin αIIbβ3 provides a ligand recognition and binding domain for the γ-chain of fibrinogen that is independent of platelet activation. Blood 1996, 87:592-601.
18. 2+ binding site of the β3-integrins that regulates the dissociation rate for RGD ligands. J Biol Chem 1996, 271:21745-21751.
19. 1 integrin is a necessary co-receptor for collagen-induces activation of syk and the subsequent phosphorylation of phospholipase Cγ2 in platelets. J Biol Chem 1996, 271:26668-26676. This study orders Syk and phospholipase Cγ2 activation and demonstrates the role of Syk in platelet aggregation induced by collagen.
20. Zhang J, Zhang J, Shattil SJ, Cunningham MC, Rittenhouse SE: Phosphoinosltide 3-kinase gamma and p85/phosphoinositide 3-kinase in platelets: relative activation by thrombin receptor or betaphorbol myristate acetate and roles in promoting the ligand-binding function of alphaIIbbeta3 integrin. J Biol Chem 1996, 271:6265-6272.
21. Shock DD, Wencel-Drake JD, Parise LV: Ras activation in platelets after stimulation of the thrombin receptor, thromboxane A, receptor or protein kinase C. Biochem J 1997, 321:525-530. This paper demonstrates that, despite older reports to the contrary, Ras is present in platelets and activated downstream of PKC during platelet activation.
22. 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.
23. Hughes PE, Diaz-Gonzalez F, Leong L, Wu C, McDonald JA, Shattil SJ, Ginsberg MH: Breaking the integrin hinge: a defined structural constraint regulates integrin signaling. J Biol Chem 1996, 271:6571-6574. This important paper demonstrates that the α and β cytoplasmic domains probably interact via a salt bridge that maintains the integrin in a resting state that cannot bind macromolecular ligands, until disrupted by inside-out signaling.
24. 3: a ternary complex of the integrin α and β subunits and a divalent cation. J Biol Chem 1996, 271:6017-6026. This interesting study shows that the αIIb cytoplasmic domain has a functional cation-binding site and that peptides mimicking the two cytoplasmic domains interact independent of cations.
25. Boudignon-Proudhon C, Patel PM, Parise LV: Phorbol ester enhances integrin αIIbβ3-dependent adhesion of human erythroleukemic cells to activation-dependent monoclonal antibodies. Blood 1996, 87:968-976.
26. Loh E, Qi W, Vilaire G, Bennett JS: Effect of cytoplasmic domain mutations on the agonist-stimulated ligand binding activity of the platelet integrin αIIbβ3. J Biol Chem 1996, 271:30233-30241. This study is very significant because this is the first time a cell line is identified in which expressed wild-type αIIbβ3 can be activated by an agonist via a signal transduction-mediated mechanism to bind soluble fibrinogen.
27. O'Toole TE, Katagiri Y, Faull RJ, Peter K, Tamura R, Quaranta V, Loftus JC, Shattil SJ, Ginsberg MH: Integrin cytoplasmic domains mediates inside-out signal transduction. J Cell Biol 1994, 124:1047-1059.
28. Chen Y-P, O'Toole TE, Shiple YT, Forsyth J, LaFlamme SE, Yamada KM, Shattil SJ, Ginsberg MH: "Inside-out" signal transduction inhibited by isolated integrin cytoplasmic domains. J Biol Chem 1994, 269:18307-18310.
29. 3 by using cell-permeable peptide analogs. Proc Natl Sci U S A 1996, 93:11819-11824. In a novel approach, cell permeable peptides containing a specific region of the β3 cytoplasmic domain are found to inhibit αIIbβ3-mediated cell adhesion. The corresponding β1 cytoplasmic domain does not substitue and 2 tyrosine residues appear critical for activity of the β3 peptide.
30. Baker EK, Tozer EC, Pfaff M, Sanfors SJ, Loftus JC, Ginsberg MH: A genetic analysis of integrin function: Glanzmann thrombasthenia in vitro. Proc Natl Acad Sci U S A 1997, 94:1972-1978. In this study, an interesting, nonbiased approach involving chemical mutagenesis is introduced to identify not only sites in αIIbβ3 but also signaling molecules involved in integrin activation.
31. Hughes PE, Renshaw MW, Pfaff M, Forsyth J, Keivens VM, Schwartz MA, Ginsberg MH: Suppression of integrin activation: a novel function of a Ras/Raf-initiated MAP kinase pathway. Cell 1997, 88:521-530. In this intriguing study it is demonstrated that Ras or Raf expression suppresses the activation state of an αIIbβ3 chimera that normally exists in an energy-dependent, active conformation, suggesting that the Ras-Raf-MAPK pathway inhibits integrin activation.
32. Zhang Z, Vuori K, Wang H-G, Reed JC, Ruoslahti E: Integrin activation by R-ras. Cell 1996, 85:61 -69. This study is the first to demonstrate the activation of αIIbβ3 in CHO cells potentially via a signal transduction mechanism due to the overexpression of recombinant R-ras.
33. 3 subunit J Cell Biol 1995, 131:807-816. A novel protein is identified by the yeast-two hybrid system that binds to the β3 cytoplasmic domain and is expressed in platelets.
34. 3-endonexin. J Biol Chem 1997, 272:7693-7698.
35. Kashiwagi H, Eigenthaler E, Schwartz MA, Davis KA, Ginsberg MH, Shattil SJ: Affinity modulation of platelet integrin αIIbβ3 by β3-endonexin, a selective binding partner of the β3 Integrin cytoplasmic tall. J Cell Biol 1997, 137:1433-1443. In this study it is shown that overexpression of recombinant β3-endonexin in CHO cells activates αIIbβ3, suggesting that this protein may play a similar role in platelets.
36. Naik UP, Patel PM, Parise LV: Identification of a novel calcium-binding protein that Interacts with the integrin αIIb cytoplasmic domain. J Biol Chem 1997, 272:4651-4654. A novel protein is described that binds to the αIIb cytoplasmic domain and is homologous to the regulatory proteins calcineurin B and calmodulin.
37. Frelinger AL 3d, Du XP, Row EF, Ginsberg MH: Monoclonal antibodies to ligand-occupied conformers of integrin αIIbβ3 (glycoprotein IIb-IIIa) alter receptor affinity, specifity, and function. J Biol Chem 1991, 266:17106-17111.
38. 3, and Its ligand and induces selective movements of ligand-occupied Integrln. J Biol Chem 1996, 271:7004-7011. Results of this study suggest that membrane-skeletal GP IIb-IIIa binds fibrinogen and triggers cytoskeletal reorganization, resulting in selective movement of occupied integrin.
39. Fox JE, Lipfert L, Clark EA, Reynolds CC, Austin, CD, Brugge JS: On the association of GP IIb-IIIa, pp60c-src, pp62c-yes, and the p21 ras GTPase-activating protein with the membrane skeleton. J Biol Chem 1993, 268:25973-25984.
40. Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K: Interaction of plasma membrane fibronectin receptor with talin: a transmembrane linkage. Nature 1986, 320:531-533.
41. 3. J Biol Chem 1996, 271:16416-16421. Although talin was known to interact with the β3 cytoplasmic domain, this paper also describes a direct interaction with the αIIb cytoplasmic domain.
42. Hartwig JH, Kung S, Kovacsovics T, Janney PA, Cantley LC, Stossel TP, Toker A: D3 phospoinositides and outside-in integrin signaling by glycoprotein IIb-IIIa mediate platelet actin assembly and filopodial extension induced by phorbol 12-myristate 13-acetate. J Biol Chem 1996, 271:32986-32993.
43. Law DA, Nannizzi-Alaimo L, Phillips DR: Outside-in integrin signal transduction: αIIbβ3-(GPIIb-IIIa) tyrosine phosphorylation Induced by platelet aggregation. J Biol Chem 1996, 271:10811-10815. Phosphorylation of the β3 subunit of aIIbβ3 on tyrosine is detected for the first time in aggregated platelets and tyrosine phosphorylated peptides are found to bind the signaling molecules SHC and GRB2, suggesting potential mechanisms of outside-in signaling.
44. Rooney MM, Parise LV, Lord ST: Dissecting clot retraction and platelet aggregation: clot retraction does not require an Intact fibrinogen γ chain C terminus. J Biol Chem 1996, 271:8553-8555. Recombinant fibrinogen lacking the last four residues of the γ-chain does not support platelet aggregation but does support normal clot retraction.
45. Holmaback K, Danton MJ, Suh TT, Daughterly CC, Degen JL: Impaired platelets aggregation and sustained bleeding in mice lacking the fibrinogen motif bound by integrin αIIbβ3. EMBO J 1996, 15:5760-5771. Transgenic mice expressing fibrinogen lacking the last five residues of the γ-chain have highly defective platelet aggregation but normal clot retraction.
46. 3 (platelet glycoprotein IIb/IIIa) and the cellular retraction of fibrin clots. J Biol Chem 1997, 272:1694-1702.
47. Wencel-Drake JD, Boundignon-Proudhon C, Dieter MG, Criss AB, Parise LV: Internalization of bound fibrinogen modulates platelet aggregation. Blood 1996, 87:602-612. A study that shows a fundamental, previously unappreciated role that fibrinogen internalization may play in regulating platelet reactivity.
48. Diaz-Gonzalez F, Forsyth J, Steiner B, Ginsberg MH: Trans-dominant Inhibition of integrin function. Mol Biol Cell 1996, 7:1939-1951. This important study demonstrates that ligand occupancy of one integrin in a cell can affect the function of other integrins, most likely due to a competition between β cytoplasmic domains for limited cellular factors.