Negative feedback regulation of human platelets via autocrine activation of the platelet-derived growth factor alpha-receptor
| Autor: | O K Havnen, F S Vassbotn, H Holmsen, C H Heldin |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Autophosphorylation Tyrosine phosphorylation Cell Biology Biology Biochemistry Cell biology chemistry.chemical_compound Thrombin Endocrinology chemistry Cell surface receptor Internal medicine medicine biology.protein Platelet Platelet activation Autocrine signalling Molecular Biology Platelet-derived growth factor receptor medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 269:13874-13879 |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/s0021-9258(17)36728-5 |
| Popis: | Human platelets contain platelet-derived growth factor (PDGF) in their alpha-granules which is released during platelet exocytosis. We show by immunoprecipitation and 125I-PDGF binding experiments that human platelets have functionally active PDGF alpha-receptors, but not beta-receptors. The PDGF alpha-receptor (PDGFR-alpha) was identified as a 170-kDa glycosylated protein-tyrosine kinase as found in other cell types. Stimulation of platelets with 0.1 unit/ml thrombin resulted in a significant increase (2-5-fold) of the tyrosine phosphorylation of the PDGFR-alpha, as determined by immunoprecipitation with phosphotyrosine antiserum as well as with PDGFR-alpha antiserum. The observed thrombin-induced autophosphorylation of the PDGFR-alpha was inhibited by the addition of a neutralizing monoclonal PDGF antibody. Thus, our results suggest that the platelet PDGFR-alpha is stimulated in an autocrine manner by PDGF secreted during platelet activation. Preincubation of platelets with PDGF inhibited thrombin-induced platelet aggregation and secretion of ATP + ADP and beta-hexosaminidase. Thrombin-induced platelet aggregation was also reversed when PDGF was added 30 s after thrombin stimulation. Inhibition of the autocrine PDGF pathway during platelet activation by the PDGF antibody led to a potentiation of thrombin-induced beta-hexosaminidase secretion. Thus, the PDGFR-alpha takes part in a negative feedback regulation during platelet activation. Our demonstration of PDGF alpha-receptors on human platelets and its inhibitory function during platelet activation identifies a new possible role of PDGF in the regulation of thrombosis. |
| Databáze: | OpenAIRE |
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