Ligands "activate" integrin αIIbβ3 (platelet GPIIb-IIIa)

Xiaoping Du, Edward F. Plow, Andrew L. Frelinger, Timothy E. O'Toole, Joseph C Loftus, Mark H. Ginsberg

Research output: Contribution to journalArticle

387 Citations (Scopus)

Abstract

Integrin αIIbβ3 (platelet GPllb-Illa) binds fibrinogen via recognition sequences such as Arg-Gly-Asp (RGD). Fibrinogen binding requires agonist activation of platelets, whereas the binding of short synthetic RGD peptides does not. We now find that RGD peptide binding leads to changes in αIIbβ3 that are associated with acquisition of high affinity fibrinogen-binding function (activation) and subsequent platelet aggregation. The structural specificities for peptide activation and for inhibition of ligand binding are similar, indicating that both are consequences of occupancy of the same site(s) on αIIbβ3 Thus, the RGD sequence is a trigger of high affinity ligand binding to αIIbβ3 and certain RGD-mimetics are partial agonists as well as competitive antagonists of integrin function.

Original languageEnglish (US)
Pages (from-to)409-416
Number of pages8
JournalCell
Volume65
Issue number3
DOIs
StatePublished - May 3 1991
Externally publishedYes

Fingerprint

Platelets
Integrins
Fibrinogen
Blood Platelets
Chemical activation
Ligands
Platelet Activation
Platelet Aggregation
Agglomeration
Peptides
arginyl-glycyl-aspartic acid

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Du, X., Plow, E. F., Frelinger, A. L., O'Toole, T. E., Loftus, J. C., & Ginsberg, M. H. (1991). Ligands "activate" integrin αIIbβ3 (platelet GPIIb-IIIa). Cell, 65(3), 409-416. https://doi.org/10.1016/0092-8674(91)90458-B

Ligands "activate" integrin αIIbβ3 (platelet GPIIb-IIIa). / Du, Xiaoping; Plow, Edward F.; Frelinger, Andrew L.; O'Toole, Timothy E.; Loftus, Joseph C; Ginsberg, Mark H.

In: Cell, Vol. 65, No. 3, 03.05.1991, p. 409-416.

Research output: Contribution to journalArticle

Du, X, Plow, EF, Frelinger, AL, O'Toole, TE, Loftus, JC & Ginsberg, MH 1991, 'Ligands "activate" integrin αIIbβ3 (platelet GPIIb-IIIa)', Cell, vol. 65, no. 3, pp. 409-416. https://doi.org/10.1016/0092-8674(91)90458-B
Du X, Plow EF, Frelinger AL, O'Toole TE, Loftus JC, Ginsberg MH. Ligands "activate" integrin αIIbβ3 (platelet GPIIb-IIIa). Cell. 1991 May 3;65(3):409-416. https://doi.org/10.1016/0092-8674(91)90458-B
Du, Xiaoping ; Plow, Edward F. ; Frelinger, Andrew L. ; O'Toole, Timothy E. ; Loftus, Joseph C ; Ginsberg, Mark H. / Ligands "activate" integrin αIIbβ3 (platelet GPIIb-IIIa). In: Cell. 1991 ; Vol. 65, No. 3. pp. 409-416.
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