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

Authors

Paul F. Bray, University of California Medical Center, San FranciscoFollow
Jean-Philippe Rosa, University of Texas Health Science CenterFollow
Vishwanath R. Lingappa, University of California Medical Center, San Francisco
Yuet W. Kan, University of California Medical Center, San FranciscoFollow
Rodger P. McEver, University of Texas Health Science CenterFollow
Marc A. Shuman, University of California Medical Center, San FranciscoFollow

Document Type

Article

Publication Date

3-1986

Comments

This article has been peer reviewed. It is the author’s final published version in Proceedings of the National Academy of Sciences of the United States of America, Volume 83, Issue 5, March 1986, Pages 1480-4.

The published version is available here. Copyright © National Academy of Sciences

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.

Recommended Citation

Bray, Paul F.; Rosa, Jean-Philippe; Lingappa, Vishwanath R.; Kan, Yuet W.; McEver, Rodger P.; and Shuman, Marc A., "Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa." (1986). Cardeza Foundation for Hematologic Research. Paper 16.
https://jdc.jefferson.edu/cardeza_foundation/16