Role of fibrinogen α and γ chain sites in platelet aggregation

David Farrell, Perumal Thiagarajan, Dominic W. Chung, Earl W. Davie

Research output: Contribution to journalArticle

272 Citations (Scopus)

Abstract

Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein Hb-IIIa (integrin αIIbβ3). Peptides containing the amino acid sequence RGD derived from the α chain (residues α95-97 and residues α572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the γ chain of Fbg (residues γ400-411) inhibit these interactions. To determine the role of these sequences in intact Fbg, recombinant human Fbg (rFbg), mutant rFbgs with an RGD → RGE substitution at either position α97 or α574, and a rFbg γ′-containing variant that has a carboxyl-terminal interruption in the HHLGGAKQAGDV sequence have been expressed in transfected BHK cells. Purified rFbg and the two RGE mutant Fbgs were similar to plasma Fbg in platelet aggregation assays. In contrast, the γγ variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the γ chain of Fbg is essential for optimal platelet aggregation and that the α-chain RGD sequences are neither necessary nor sufficient for platelet aggregation.

Original languageEnglish (US)
Pages (from-to)10729-10732
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number22
StatePublished - 1992
Externally publishedYes

Fingerprint

Platelet Aggregation
Fibrinogen
Integrin beta3
Integrins
Amino Acid Sequence
Peptides

Keywords

  • Expression
  • Hemostasis
  • Mutagenesis
  • Thrombosis
  • Transfection

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Role of fibrinogen α and γ chain sites in platelet aggregation. / Farrell, David; Thiagarajan, Perumal; Chung, Dominic W.; Davie, Earl W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 22, 1992, p. 10729-10732.

Research output: Contribution to journalArticle

Farrell, David ; Thiagarajan, Perumal ; Chung, Dominic W. ; Davie, Earl W. / Role of fibrinogen α and γ chain sites in platelet aggregation. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 22. pp. 10729-10732.
@article{554222497d8c4c09ae3e0922143970d7,
title = "Role of fibrinogen α and γ chain sites in platelet aggregation",
abstract = "Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein Hb-IIIa (integrin αIIbβ3). Peptides containing the amino acid sequence RGD derived from the α chain (residues α95-97 and residues α572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the γ chain of Fbg (residues γ400-411) inhibit these interactions. To determine the role of these sequences in intact Fbg, recombinant human Fbg (rFbg), mutant rFbgs with an RGD → RGE substitution at either position α97 or α574, and a rFbg γ′-containing variant that has a carboxyl-terminal interruption in the HHLGGAKQAGDV sequence have been expressed in transfected BHK cells. Purified rFbg and the two RGE mutant Fbgs were similar to plasma Fbg in platelet aggregation assays. In contrast, the γγ variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the γ chain of Fbg is essential for optimal platelet aggregation and that the α-chain RGD sequences are neither necessary nor sufficient for platelet aggregation.",
keywords = "Expression, Hemostasis, Mutagenesis, Thrombosis, Transfection",
author = "David Farrell and Perumal Thiagarajan and Chung, {Dominic W.} and Davie, {Earl W.}",
year = "1992",
language = "English (US)",
volume = "89",
pages = "10729--10732",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "22",

}

TY - JOUR

T1 - Role of fibrinogen α and γ chain sites in platelet aggregation

AU - Farrell, David

AU - Thiagarajan, Perumal

AU - Chung, Dominic W.

AU - Davie, Earl W.

PY - 1992

Y1 - 1992

N2 - Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein Hb-IIIa (integrin αIIbβ3). Peptides containing the amino acid sequence RGD derived from the α chain (residues α95-97 and residues α572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the γ chain of Fbg (residues γ400-411) inhibit these interactions. To determine the role of these sequences in intact Fbg, recombinant human Fbg (rFbg), mutant rFbgs with an RGD → RGE substitution at either position α97 or α574, and a rFbg γ′-containing variant that has a carboxyl-terminal interruption in the HHLGGAKQAGDV sequence have been expressed in transfected BHK cells. Purified rFbg and the two RGE mutant Fbgs were similar to plasma Fbg in platelet aggregation assays. In contrast, the γγ variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the γ chain of Fbg is essential for optimal platelet aggregation and that the α-chain RGD sequences are neither necessary nor sufficient for platelet aggregation.

AB - Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein Hb-IIIa (integrin αIIbβ3). Peptides containing the amino acid sequence RGD derived from the α chain (residues α95-97 and residues α572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the γ chain of Fbg (residues γ400-411) inhibit these interactions. To determine the role of these sequences in intact Fbg, recombinant human Fbg (rFbg), mutant rFbgs with an RGD → RGE substitution at either position α97 or α574, and a rFbg γ′-containing variant that has a carboxyl-terminal interruption in the HHLGGAKQAGDV sequence have been expressed in transfected BHK cells. Purified rFbg and the two RGE mutant Fbgs were similar to plasma Fbg in platelet aggregation assays. In contrast, the γγ variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the γ chain of Fbg is essential for optimal platelet aggregation and that the α-chain RGD sequences are neither necessary nor sufficient for platelet aggregation.

KW - Expression

KW - Hemostasis

KW - Mutagenesis

KW - Thrombosis

KW - Transfection

UR - http://www.scopus.com/inward/record.url?scp=0026476365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026476365&partnerID=8YFLogxK

M3 - Article

VL - 89

SP - 10729

EP - 10732

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 22

ER -