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PMID: 3006053 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 5 ·1986-03-00 ·Pages 1480-4

Bray PF, Rosa JP, Lingappa VR, Kan YW, McEver RP, Shuman MA

Abstract

Congenital absence of platelet glycoproteins IIb and IIIa (GPIIb and GPIIIa) results in a severe bleeding disorder characterized by defective platelet aggregation and failure of fibrinogen to bind to platelets. GPIIb is a two-chain protein containing disulfide-linked alpha and beta subunits. GPIIb and GPIIIa are present as a heterodimeric, noncovalent complex in the platelet plasma membrane and function as the fibrinogen receptor. To characterize synthesis of these two proteins, RNA isolated from a human leukemia cell line that contains GPIIb and GPIIIa was translated in a wheat germ cell-free system. Polyclonal antibodies specific for each protein immunoprecipitated distinct [35S]methionine-labeled precursors, indicating that GPIIb and GPIIIa are translated from separate mRNAs. Moreover, using specific antibodies against either intact unreduced GPIIb or the beta subunit, we obtained evidence for synthesis of a common polypeptide precursor for GPIIb alpha and GPIIb beta. Based on experiments using microsomal membranes, it appears that GPIIb is integrated into the platelet membrane with little or no cytoplasmic component. These results suggest that precursors of GPIIb and GPIIIa may be encoded by separate genes and that each precursor is processed before delivery to the plasma membrane.

MeSH Terms
Cell Line Cells, Cultured Endoplasmic Reticulum/metabolism Glycoproteins/biosynthesis,immunology Humans Immunologic Techniques Intracellular Membranes/metabolism Leukemia, Erythroblastic, Acute Membrane Proteins/biosynthesis,immunology Molecular Weight Platelet Membrane Glycoproteins Protein Biosynthesis Protein Precursors/metabolism Protein Processing, Post-Translational RNA, Messenger/metabolism Receptors, Cell Surface/biosynthesis,immunology
Chemicals
Glycoproteins Membrane Proteins Platelet Membrane Glycoproteins Protein Precursors RNA, Messenger Receptors, Cell Surface
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bray P F
Rosa J P
Lingappa V R
Kan Y W
McEver R P
Shuman M A
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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.83.5.1480
Published
1986-03-00
Pages
1480-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323100
Subset
IM
Grants
NCI NIH HHS · CA 09436A · United States
NIGMS NIH HHS · GM 31626 · United States
NHLBI NIH HHS · HL 33277 · United States
External Links
PubMed source DOI: 10.1073/pnas.83.5.1480 PMC Full Text View journal details
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