Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the role of protein phosphorylation in erythropoietin (EPO)-mediated signal transduction, we examined the effects of tyrosine phosphatase and tyrosine and serine-threonine kinase inhibitors as well as activators of serine kinases on DNA synthesis and cell proliferation in the murine EPO-dependent cell line HCD-57. HCD-57 cells were obtained synchronized in G0 by centrifugal elutriation, and DNA synthesis was measured by incorporation of labeled thymidine into DNA. Half-maximal DNA synthesis was stimulated by 0.001 U/ml of EPO. Sodium orthovanadate (Na3VO4), a tyrosine phosphatase inhibitor, at 5 microM potentiated a subsaturating concentration of EPO. Na3VO4 alone stimulated HCD-57 DNA synthesis at concentrations of 0.1-20 microM. Zinc chloride, another tyrosine phosphatase inhibitor, also stimulated HCD-57 DNA synthesis at concentrations of 50-100 microM. Genistein, a tyrosine kinase inhibitor, blocked the effect of EPO at a concentration of 5 micrograms/ml. Bryostatin, a protein kinase C (PKC) activator, stimulated DNA synthesis in HCD-57 cells at concentrations of 10(-9)-10(-10) M, whereas the phorbol ester, phorbol 12,13-dibutyrate (PDBu), was stimulatory only at a concentration of 10(-11) M. Staurosporine, a PKC inhibitor, blocked the effect of EPO at a concentration of 10(-7) M, and H-7, a nonspecific protein kinase inhibitor, was not inhibitory. These agents also had similar effects on the in vitro proliferation of HCD-57 cells. Taken together, the data indicate that the EPO-mediated transition from G0 to S phase in HCD-57 cells involves the activation of both tyrosine and serine-threonine kinases and is modulated by tyrosine phosphatase activity.
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PMID:Protein kinases and phosphatases are involved in erythropoietin-mediated signal transduction. 131 37

In previous studies we had found that at late stages of development, when the early patterning control mechanism have ceased to act, the chick limb bud is able to form fully differentiated extradigits by subjecting the interdigital spaces to ectoderm removal. In this study we attempted to mimic this phenomenon by using local microinjections of substances which presumably have a biological action on the interdigital mesenchyme. Microinjection of staurosporine results in the formation of fully differentiated extradigits. The action of this drug appears to be due to the induction of chondrogenesis after the inhibition of the protein kinase C. Zinc chloride administration also causes ectopic chondrogenesis but it seems to act by arresting the interdigital cell death program through endonuclease inhibition. A clear differentiation of the zinc-induced cartilages into extradigits was no detected. This can be explained by the accompanying damage caused by zinc in the growing limb mesenchyme as deduced by the high incidence of hypophalangy in the normal digits. Both TGF beta 1 and TGF beta 2 have a weak effect as inducers of interdigital chondrogenesis; presumably they act by inducing chondrogenetic differentiation. Neither FGF nor EGF has any effect when administered by local microinjection. These results show that ectopic interdigital chondrogenesis induced by drug administration results in the differentiation of extradigits. This suggests that once a cartilage is formed in the autopodium it triggers a new signalling stage which leads to the morphogenesis of a digit. This morphogenetic process involves the patterning of skeleton, joints and tendons. In accordance with these observations, it can be proposed that early patterning of the limb results in the establishment of an autopodium with a defined but still plastic skeletal distribution pattern, while morphogenesis of each autopodial element would take place at a second stage by the activation of new signalling processes.
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PMID:In vivo experimental induction of interdigital tissue chondrogenesis in the avian limb bud results in the formation of extradigits. Effects of local microinjection of staurosporine, zinc chloride and growth factors. 830 89

Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, causes increased levels of tyrosine phosphorylation and blocks, at noncytotoxic concentrations, the differentiative response of rat pheochromocytoma (PC12) cells to beta-nerve growth factor (beta NGF) and basic fibroblast growth factor (bFGF) in a reversible manner. It also prevents growth factor-induced neurite proliferation in primed cells and causes the retraction of previously formed neurites, even in the presence of beta NGF or bFGF. It is equally effective in blocking neurite proliferation by 8-Br-cAMP. Zinc chloride and ammonium molybdate, two other inhibitors of tyrosine phosphatases, also cause parallel decreases in neurite proliferation. Orthovanadate generally reduces the transcription of immediate early response genes (TIS 8 and c-fos) and secondary response genes (ornithine decarboxylase (ODC), acetyl-cholinesterase (AChE) and SCG 10) induced by beta NGF, bFGF, EGF, and PMA, albeit in a variable fashion. There was no observed effect on the kinetics of expression as judged by TIS 8 induction by beta NGF and protein kinase C (PKC) downregulation did not change the levels of inhibition by orthovanadate seen in control cells. Orthovanadate does not affect the production of diacylglycerol induced by beta NGF or bFGF. These observations are consistent with the view that growth factor stimulation of differentiation in PC12 cells involves at least one other PKC independent pathway, and that cAMP and PMA (and their active analogs) activate tyrosine kinases (albeit probably secondarily), which are at least partially responsible for their actions. Although the exact site(s) of action of orthovanadate that lead to the inhibition of growth factor-induced neurite proliferation are unknown, the results presented suggest that it prolongs tyrosine phosphorylations by nonreceptor tyrosine kinases that act downstream from the receptor kinases.
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PMID:Effect of nerve growth factor and fibroblast growth factor on PC12 cells: inhibition by orthovanadate. 846 55