Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intact human platelets, terminally differentiated cells with no growth potential, were found to possess unusually high levels of tyrosine-specific protein phosphorylation. The physiological platelet activator thrombin transiently elevated platelet phosphotyrosine content, apparently through stimulation of one or more tyrosine-specific protein kinases. Immunoblotting with antiphosphotyrosine antiserum showed that thrombin caused dramatic changes in the tyrosine phosphorylation of a number of individual protein bands and that these changes occurred in three distinct temporal waves. Most but not all of the protein bands phosphorylated at tyrosine in response to thrombin were also tyrosine phosphorylated in response to chilling or the combination of ionophore A23187 and tetradecanoylphorbol acetate. Thrombin stimulated the phosphorylation of the tyrosine kinase pp60c-src, primarily at Ser-12 and Tyr-527, although the effects of these phosphorylations on platelet pp60c-src function were not apparent. Together, these results suggest that tyrosine-specific protein kinases of uncertain identity are involved in signal transduction in platelets.
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PMID:Platelet tyrosine-specific protein phosphorylation is regulated by thrombin. 246 41

The binding of vasoactive peptides to their respective G protein-coupled receptors has been implicated in the pathogenesis of vascular smooth muscle cell proliferation, leading to the development of hypertension, arteriosclerosis, and restenosis after vascular injury. We previously showed that the cytosolic tyrosine kinase pp60c-src is crucial for angiotensin II (ANG II)-induced activation of the protooncogene p21ras. Therefore, we investigated the role of pp60c-src and p21ras in rat aortic smooth muscle cell proliferation induced by several G protein-coupled receptors. ANG II, endothelin-1, or thrombin increased cell proliferation and DNA synthesis. Electroporation of anti-pp60c-src antibodies into cells abolished proliferation in response to these G protein-coupled receptor ligands but not in response to platelet-derived growth factor-BB (PDGF-BB). In contrast, electroporation of anti-p21ras antibody completely blocked DNA synthesis and cell proliferation in response to ANG II, endothelin-1, thrombin, and PDGF-BB. Our data indicate that the pp60c-src tyrosine kinase is necessary and specific for vascular smooth muscle cell proliferation and DNA synthesis in response to G protein-coupled receptors but not classic growth factor receptors.
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PMID:G protein-coupled receptors control vascular smooth muscle cell proliferation via pp60c-src and p21ras. 922 31