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

Mitogen-activated protein (MAP) kinases are regarded as switch kinases in the phosphorylation cascade initiated by various agonists. We have investigated whether endothelins (ET), which are constrictor and mitogenic isopeptides, can increase MAP kinase activity in rat mesangial cells, using bovine myelin basic protein (MBP) as a substrate for an in vitro kinase assay. Treatment of quiescent mesangial cells with ET-1 rapidly stimulated a kinase activity which phosphorylated exogenous MBP. This stimulation was dose-dependent, with threshold responses at 1 nM-ET-1. Epidermal growth factor and thrombin also activated this kinase in mesangial cells. We also examined the ET signal transduction pathways leading to activation of MBP kinase. Pertussis toxin had no effect on ET-stimulated MBP kinase activity. Stimulation of protein kinase C by phorbol ester increased MBP kinase activity, and down-regulation of PKC partially inhibited ET-stimulated MBP kinase as well as phorbol ester-stimulated MBP kinase activity. Interestingly, genestein, an inhibitor of protein tyrosine kinases, partially inhibited MBP kinase stimulated by ET but not by phorbol esters. These results suggest that ET stimulates MBP kinase activity in rat mesangial cells via at least two pathways: one which is protein kinase C-dependent and a second one that involves a protein tyrosine kinase. Finally, by raising rabbit antibodies against the two forms of MAP kinase, p44mapk and p42mapk, we demonstrated that both isoforms are expressed in mesangial cells. Antibody alpha 1 Cp42 specifically immunoprecipitated p42mapk and allowed us to demonstrate that ET stimulates MBP kinase activity in the p42mapk immunocomplex. In conclusion, we have provided evidence that, in rat mesangial cells, MAP kinases are rapidly activated by ET-1, a regulatory process that involves at least protein kinase C activation and also a contribution of a tyrosine kinase not yet characterized.
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PMID:Endothelin rapidly stimulates mitogen-activated protein kinase activity in rat mesangial cells. 128 Jan 3

An LM immunocytochemical study has investigated the patterns of staining in turtle retina with monoclonal antibodies to the alpha, beta and gamma isozymes of protein kinase C. The protein kinase C-gamma antibody reveals cells in the ganglion cell layer, occasional amacrine cells and faint banding in strata 2 and 4 of the inner plexiform layer. The protein kinase C-beta antibody stains primarily amacrine cells that have dendrites running in strata 2, in 4 close to the 3/4 border and on the 4/5 border of the inner plexiform layer. Protein kinase C-alpha immunoreactivity is seen in a population of bipolar cells. The latter are characterized by stained axon terminals in strata 3 and 4 of the inner plexiform layer. A type of amacrine cell, different from those seen with the other antibodies, is also immunoreactive to protein kinase C-alpha. EM immunocytochemistry (using a polyclonal antibody) reveals protein kinase C immunoreactivity in photoreceptor cells, bipolar cells, amacrine cells and ganglion cells. In photoreceptors protein kinase C immunoreactivity occurs as patchy staining associated with vesicles and the plasmalemma in pedicles and telodendria. Some varieties of bipolar cell display protein kinase C reaction product throughout the entire cell. Their dendrites contact photoreceptor pedicles at wide-cleft basal junctions and ribbon and non-ribbon related narrow cleft junctions. A few lateral elements per cone or rod pedicle are always protein kinase C-immunoreactive. Amacrine and ganglion cells typically show small clumps of protein kinase C immunoreactivity around vesicles and close to the postsynaptic membranes. Synaptic boutons of some varieties of amacrine cell stain more uniformly. Protein kinase C-immunoreactive bipolar cells are most commonly presynaptic in stratum 4 of the inner plexiform layer, while protein kinase C-immunoreactive amacrine cells are both pre- and postsynaptic throughout strata 1, 2, 3 and 4. Stratum 5 appears to be almost devoid of protein kinase C-immunoreactive neural profiles.
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PMID:Immunocytochemical staining with antibodies against protein kinase C and its isozymes in the turtle retina. 128 73

Two main forms of protein kinase C (PKC 1 and PKC 2) are detected in homogenates of rat hepatocytes using DEAE-cellulose column chromatography. The activity of these forms paradoxically, is rapidly decreased by treatment in vivo with phorbol myristate acetate (PMA). The dose-response curves to PMA for decreasing the activities of PKC 1 and 2 were shifted to the right by the potent and selective PKC inhibitors, staurosporine and calphostin-C. The decreases induced by 100 nM PMA were dose-dependently blocked by these inhibitors. It is concluded that activation of PKC is required and precedes such decreases in activity induced by the active phorbol ester.
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PMID:Staurosporine and calphostin-C inhibit the phorbol ester-induced decrease of protein kinase C activity in rat hepatocytes. 128 16

The precursors of all blood cell lineages are contained within the 1-3% of bone marrow cells which express the CD34 antigen, and this population can reconstitute the hematopoietic system of lethally irradiated animals and humans. A potential regulatory role for the CD34 antigen in progenitor cell function and differentiation was indicated by our recent findings that the CD34 antigen can be phosphorylated in vivo to high stoichiometry in primitive CD34+ cell-lines by activated protein kinase C. To exclude the possibility that these effects were restricted to cell-lines, we have performed similar experiments on fresh cells from a patient with drug-resistant acute lymphoblastic leukemia. Similar to our previous findings, we found the CD34 antigen to be hyperphosphorylated in lymphoblasts labeled in the presence of active phorbols. The same peptides which were hyperphosphorylated in phorbol-stimulated cell-lines were also phosphorylated in phorbol-stimulated lymphoblasts. These data indicate that CD34 is a substrate molecule for PKC in fresh CD34+ lymphoblasts and underline the role of modulators of PKC activity in the biology of primitive leucocytes.
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PMID:Activated protein kinase C directly phosphorylates the CD34 antigen in acute lymphoblastic leukemia cells. 128 64

PKC-modulators represent valuable additions to the arsenal of anti-tumor agents. They act as antiproliferative agents and are useful in overcoming drug-resistance by inhibiting mdr-mediated drug efflux. They increase the cytotoxicity to platinum complexes (and other DNA-damaging agents), probably by interfering with drug-induced detoxification and repair mechanisms. PKC-modulators are potentially active in overcoming ras-induced cis-platinum-resistance by antagonizing p21ras functions.
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PMID:Protein kinase C modulation. 128 56

Conformational restrictions of sangivamycin, a rather selective inhibitor of PKC, could be achieved by the use of the steric effect and the gauche effect of the substituents on the ribofuranose moiety. The conformational deviations obtained by these methods were found to nicely correlate with the inhibitory ability of PKC.
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PMID:A study on conformationally restricted sangivamycins and their inhibitory abilities of protein kinases. 128 6

There have been an increasing number of reports describing a pivotal role for phosphorylation in cellular responses for cell differentiation and proliferation. We examined an immunocytochemical expression of protein kinase C(PKC) isozymes (type I, II, and III) in 22 leukemia-lymphoma cell lines. Of these cell lines, 21 expressed type II PKC and 17 showed the co-expression of both types II and III PKC in varying degree. The cell line without PKC activity showed far less [3H]-TdR uptake and no heterotransplantation in nude mice. Types II and III PKC appear to relate to cell proliferation in certain leukemia-lymphoma cell lines.
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PMID:Protein kinase C isozyme expression in human leukemia-lymphoma cell lines--an immunocytochemical study. 129 30

In culture the protracted and abusive stimulation of glutamate (GLU) receptors results in neuronal death through a mechanism involving the persistent translocation of PKC and the destabilization of (Ca2+)i homeostasis [(Ca2+)i HD]. In contrast, intermittent GLU receptor use elicits a coordinated expression of immediate early genes (IEG) acting as nuclear third messenger. Brain ischemia also is known to result in the paroxysmal abusive stimulation of glutamate receptors. The glutamate receptive elements in turn degenerate largely as a function of their inability to control homeostatic Ca2+ due to the irreversible translocation of PKC. In the present study we employed an in vivo model of focal brain ischemia using the photosensitive dye, Rose bengal. With this model we sought to determine the neuroprotective actions of MK-801, a noncompetitive blocker of GLU at the NMDA-sensitive receptor and of the semisynthetic gangliosides LIGA 4 and LIGA 20 which in vitro have been demonstrated to block PKC translocation. Moreover, we sought to establish whether the persistent stimulation of ionotropic glutamate receptors would led to a change in ionotropic glutamate expression in the focal and perifocal area. Importantly, the perifocal area (i. e., the region surrounding the area of primary insult) is a region in which profound cellular reorganization occurs including neuronal death and glial proliferation and is a key region to target various neuroprotective drugs aimed at ameliorating the neurodegeneration following stroke. Receptor abuse dependent antagonists (RADA) drugs such as gangliosides selectively curtail the amplification steps that specifically differentiate signal transduction following physiological receptor use from that following pathological receptor abuse.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sequelae of biochemical events following photochemical injury of rat sensory-motor cortex: mechanism of ganglioside protection. 130 98

Protein kinase C consists of a protein family which can be classified into two major groups: Ca(2+)-dependent conventional protein kinase C and Ca(2+)-independent novel protein kinase C (nPKC). Among eight known members of protein kinase C family, we found that nPKC eta (eta) isolated from cDNA library of mouse skin, is most abundant in epithelial tissues including skin and epithelia of digestive and respiratory tracts. These data suggest potential role of this isoform in growth, differentiation and carcinogenesis of epithelial tissues.
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PMID:A Ca(2+)-independent protein kinase C, nPKC eta: its structure, distribution and possible function. 130 12

The effects of syncytiotrophoblast plasma membrane vesicles (STPM) on stimulated Jurkat leukemic T cells have been investigated. STPM inhibited IL-2 production and the expression of protein P55 of the IL-2 receptor (IL-2R P55), when Jurkat cells were stimulated by a combination of calcium ionophore A23187 (CaI) + phorbol 12-myristate 13-acetate (PMA). STPM also inhibited IL-2R P55 when cells were stimulated by PMA alone, a situation in which IL-2 production is negligible. On the other hand, STPM had no effect on the sustained mobilization of intracellular Ca2+ induced by CaI nor on the PKC-dependent CD3 down regulation induced by PMA. Finally STPM had no effect on intracellular cAMP levels. These results show that (i) the inhibitory effect of STPM on IL-2R P55 expression is independent of the inhibition of IL-2 production, and (ii) the inhibitory effects of STPM are at least partially independent of phosphatidylinositol 4,5-bisphosphate hydrolysis. They suggest that STPM affect a signaling pathway activated by PMA but possibly PKC independent.
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PMID:Inhibitory effect of human syncytiotrophoblast plasma membrane vesicles on Jurkat cells activated by phorbol ester and calcium ionophore. 130 91


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