Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa.
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.
D002460:Cell Line; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007158:Immunologic Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000276:immunology; D008970:Molecular Weight; D010980:Platelet Membrane Glycoproteins; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000276:immunology
D006023:Glycoproteins; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D011498:Protein Precursors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface