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PMID: 1438269 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Role of fibrinogen alpha and gamma chain sites in platelet aggregation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 22 ·1992-11-15 ·Pages 10729-32

Farrell DH, Thiagarajan P, Chung DW, Davie EW

Abstract

Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein IIb-IIIa (integrin alpha IIb beta 3). Peptides containing the amino acid sequence RGD derived from the alpha chain (residues alpha 95-97 and residues alpha 572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the gamma chain of Fbg (residues gamma 400-411) 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 alpha 97 or alpha 574, and a rFbg gamma'-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 gamma' variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the gamma chain of Fbg is essential for optimal platelet aggregation and that the alpha-chain RGD sequences are neither necessary nor sufficient for platelet aggregation.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Line Fibrinogen/genetics,isolation & purification,metabolism Humans Kinetics Macromolecular Substances Molecular Sequence Data Molecular Weight Mutagenesis, Site-Directed Oligodeoxyribonucleotides Platelet Aggregation Platelet Membrane Glycoproteins/metabolism Recombinant Proteins/isolation & purification,metabolism Transfection
Chemicals
Macromolecular Substances Oligodeoxyribonucleotides Platelet Membrane Glycoproteins Recombinant Proteins Fibrinogen
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Farrell D H
Department of Biochemistry, University of Washington, Seattle 98195.
Thiagarajan P
Chung D W
Davie E W
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44 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.22.10729
Published
1992-11-15
Pages
10729-32
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50415
Subset
IM
Grants
NHLBI NIH HHS · HL-16919 · United States
NHLBI NIH HHS · HL-40860 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.22.10729 PMC Full Text View journal details
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