Biosynthesis and processing of platelet GPIIb-IIIa in human megakaryocytes
| Autor: | Mark H. Ginsberg, G Marguerie, Alain Duperray, Rolande Berthier, E. F. Plow, E Chagnon, J J Ryckewaert |
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| Rok vydání: | 1987 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Glycosylation Fibrinogen receptor Population Oligosaccharides Platelet Membrane Glycoproteins Biology Platelet membrane glycoprotein Fibrinogen chemistry.chemical_compound Megakaryocyte hemic and lymphatic diseases Acetylglucosaminidase medicine Humans Platelet Monensin Protein Precursors education chemistry.chemical_classification education.field_of_study Tunicamycin Cell Membrane hemic and immune systems Articles Cell Biology Molecular biology Molecular Weight Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase medicine.anatomical_structure chemistry Biochemistry Glycoprotein Megakaryocytes Protein Processing Post-Translational circulatory and respiratory physiology medicine.drug |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.104.6.1665 |
| Popis: | Platelet membrane glycoprotein IIb-IIIa forms a calcium-dependent heterodimer and constitutes the fibrinogen receptor on stimulated platelets. GPIIb is a two-chain protein containing disulfide-linked alpha and beta subunits. GPIIIa is a single chain protein. These proteins are synthesized in the bone marrow by megakaryocytes, but the study of their synthesis has been hampered by the difficulty in obtaining enriched population of megakaryocytes in large numbers. To examine the biosynthesis and processing of GPIIb-IIIa, purified human megakaryocytes were isolated from liquid cultures of cryopreserved leukocytes stem cell concentrates from patients with chronic myelogenous leukemia. Immunoprecipitation of [35S]methionine pulse-chase-labeled cell extracts by antibodies specific for the alpha or beta subunits of GPIIb indicated that GPIIb was derived from a precursor of Mr 130,000 that contains the alpha and beta subunits. This precursor was converted to GPIIb with a half-life of 4-5 h. No precursor form of GPIIIa was detected. The glycosylation of GPIIb-IIIa was examined in megakaryocytes by metabolic labeling in the presence of tunicamycin, monensin, or treatment with endoglycosidase H. The polypeptide backbones of the GPIIb and the GPIIIa have molecular masses of 120 and 90 kD, respectively. High-mannose oligosaccharides are added to these polypeptide backbones co-translationally. The GPIIb precursor is then processed with conversion of high-mannose to complex type carbohydrates yielding the mature subunits GPIIb alpha (Mr 116,000) and GPIIb beta (Mr 25,000). No posttranslational processing of GPIIIa was detected. |
| Databáze: | OpenAIRE |
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