Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chimeric EK-receptor (EK-R), consisting of the epidermal growth factor receptor (EGF-R) extracellular binding domain and p145c-kit cytoplasmic signal-generating sequences, was fully functional in forming high and low affinity EGF binding sites and in ligand-regulated receptor and substrate phosphorylation activities. Relative to EGF-R, EK-R activation stimulated kit-characteristic phosphorylation of human 293 fibroblast substrate polypeptides. Transient coexpression of EK-R with candidate substrates resulted in ligand-induced phosphorylation of phospholipase C gamma and guanosine triphosphatase-activating polypeptide. The RAF-1 serine/threonine kinase was shown to be associated with activated EK-R, but no tyrosine phosphorylation could be detected. The faithfulness of EK-R substrate phosphorylation specificity was confirmed with stem cell factor-stimulated p145c-kit.
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PMID:Substrate phosphorylation specificity of the human c-kit receptor tyrosine kinase. 171 57

Proliferation, differentiation, and survival of erythroid progenitor cells are mainly regulated by stem cell factor (SCF) and erythropoietin (Epo). Using normal human progenitors, we analyzed the role of Ca2+-sensitive protein kinase C (PKC) subtypes and of G-protein-coupled receptor ligands on growth factor-dependent DNA synthesis. We show that stimulation of DNA synthesis by the two growth factors requires activation of PKCalpha. Inhibitors of Ca2+-activated PKC subtypes blocked the growth factor-induced 3H-thymidine incorporation. SCF and Epo caused no significant translocation of PKCalpha into the membrane, but treatment of intact cells with either of the two cytokines resulted in enhanced activity of immunoprecipitated cytosolic PKCalpha. Stimulation of PKC with the phorbol ester PMA mimicked the cytokine effect on DNA synthesis. Epo-, SCF-, and PMA-induced thymidine incorporation was potently inhibited by thrombin (half-maximal inhibition with 0.1 U/mL). This effect was mediated via the G-protein-coupled thrombin receptor and the Rho guanosine triphosphatase. Adenosine diphosphate caused a modest Ca2+-dependent stimulation of DNA synthesis in the absence of cytokines and specifically enhanced the effect of SCF. Cyclic 3', 5'-adenosine monophosphate exerted a selective inhibitory effect on Epo-stimulated thymidine incorporation. Our results define PKCalpha as major intermediate effector of cytokine signaling and suggest a role for thrombin in controlling erythroid progenitor proliferation.
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PMID:Erythropoietin- and stem cell factor-induced DNA synthesis in normal human erythroid progenitor cells requires activation of protein kinase Calpha and is strongly inhibited by thrombin. 1038 4