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

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 ..cap 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 (/sup 35/S)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, the authors obtained evidence for synthesis of a common polypeptide precursor for GPIIb..cap alpha.. and GPIIb..gamma... 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.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Univ. of California Medical Center, San Francisco
OSTI Identifier:
5622335
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. U.S.A.; (United States)
Additional Journal Information:
Journal Volume: 83:5; Journal Issue: 5
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BLOOD PLATELETS; LABELLING; GLUCOPROTEINS; BIOSYNTHESIS; LABELLED COMPOUNDS; FIBRINOGEN; LEUKEMIA; MAN; MESSENGER-RNA; METHIONINE; RECEPTORS; SULFUR 35; TUMOR CELLS; AMINO ACIDS; ANIMAL CELLS; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BLOOD COAGULATION FACTORS; BODY FLUIDS; CARBOHYDRATES; CARBOXYLIC ACIDS; COAGULANTS; DAYS LIVING RADIOISOTOPES; DISEASES; DRUGS; EVEN-ODD NUCLEI; GLOBULINS; HEMATOLOGIC AGENTS; HEMIC DISEASES; HEMOSTATICS; ISOTOPES; LIGHT NUCLEI; LIPOTROPIC FACTORS; MAMMALS; MATERIALS; MEMBRANE PROTEINS; NEOPLASMS; NUCLEI; NUCLEIC ACIDS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PRIMATES; PROTEINS; RADIOISOTOPES; RNA; SACCHARIDES; SULFUR ISOTOPES; SYNTHESIS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Bray, P F, Rosa, J P, Lingappa, V R, Kan, Y W, McEver, R P, and Shuman, M A. Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa. United States: N. p., 1986. Web. doi:10.1073/pnas.83.5.1480.
Bray, P F, Rosa, J P, Lingappa, V R, Kan, Y W, McEver, R P, & Shuman, M A. Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa. United States. https://doi.org/10.1073/pnas.83.5.1480
Bray, P F, Rosa, J P, Lingappa, V R, Kan, Y W, McEver, R P, and Shuman, M A. 1986. "Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa". United States. https://doi.org/10.1073/pnas.83.5.1480.
@article{osti_5622335,
title = {Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa},
author = {Bray, P F and Rosa, J P and Lingappa, V R and Kan, Y W and McEver, R P and Shuman, M A},
abstractNote = {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 ..cap 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 (/sup 35/S)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, the authors obtained evidence for synthesis of a common polypeptide precursor for GPIIb..cap alpha.. and GPIIb..gamma... 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.},
doi = {10.1073/pnas.83.5.1480},
url = {https://www.osti.gov/biblio/5622335}, journal = {Proc. Natl. Acad. Sci. U.S.A.; (United States)},
number = 5,
volume = 83:5,
place = {United States},
year = {Sat Mar 01 00:00:00 EST 1986},
month = {Sat Mar 01 00:00:00 EST 1986}
}