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)

Eight days after chronic constrictive sciatic nerve injury (CCI), protein kinase C gamma (PKC gamma) immunoreactivity reliably increased in the spinal cord dorsal horn of CCI rats with demonstrable thermal hyperalgesia as compared to sham-operated controls. Such PKC gamma immunostaining was observed primarily in neuronal somata (ipsilateral > contralateral, laminae I-II > III-IV), indicating postsynaptic sites of PKC gamma increases. Both the development of thermal hyperalgesia and the increase in PKC gamma immunoreactivity in CCI rats were prevented by once daily intrathecal administration with 10 nmol MK-801 for 7 days. The present results provide further evidence for a role of PKC in N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms of thermal hyperalgesia.
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PMID:Increases in protein kinase C gamma immunoreactivity in the spinal cord dorsal horn of rats with painful mononeuropathy. 859 45

1. Immunoblot experiments in rat prostatic epithelium using a non-selective antibody against protein kinase C (PKC) allowed to detect three PKC subspecies of 87.5, 55.5 and 34.6 kDa that showed higher, similar and lower immunoreactivity in the membrane than in the cytosolic compartment, respectively. 2. Specific monoclonal antisera revealed that the PKC-gamma isozyme is not expressed in the rat prostatic epithelium, whereas the PKC-beta isozyme was noted only in the cytosolic fraction showing an apparent molecular weight of 75.5 kDa. 3. Induction of diabetes by streptozotocin led to modifications in the expression of PKC isozymes so that the immunoreactivities of the 87.5- and 55.5-kDa PKC forms decreased in both cytosolic and membrane subcellular fractions to different extents. 4. The most important decrease was that of the 55.5-kDa PKC form in cytosol that returned to control values by insulin therapy, whereas PKC-beta suffered also some decrease in diabetes and increased again with insulin treatment.
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PMID:Protein kinase C isozymes in prostatic epithelial cells from normal, diabetic and insulin-treated diabetic rats. 874 55

Megakaryocytes undergo a unique differentiation program, becoming polyploid through repeated cycles of DNA synthesis without concomitant cell division. We have shown previously that phorbol 12-myristate 13-acetate (PMA) induces the Dami human megakaryocytic cell line to become polyploid and to express platelet-specific proteins, including von Willebrand factor (vWF) and glycoprotein Ib (GpIb). Phorbol esters are thought to regulate gene expression principally through the activation of protein kinase C (PKC), a family of structurally related kinases with potentially unique activation requirements and substrate specificities. A survey of PKC isoforms in Dami cells revealed that, by both Western and Northern analyses, PKC isoforms alpha, beta, delta, epsilon, eta, theta, and zeta were reproducibly detected. PKC-gamma was not detected. In order to define the role of individual PKC isoforms in megakaryocytic maturation, PMA and 2-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), a putative selective activator of the PKC-beta 1 isotype, were compared for their effects on Dami cell maturation. Treatment with either dPPA or PMA caused Dami cells to cease proliferating, to become polyploid, and to express vWF. We also examined dPPA and PMA for their ability to activate and to downregulate expression of different PKC isoforms. Fifteen-minute treatment with PMA resulted in the translocation of PKC isoforms alpha, epsilon, and theta from the cytosolic to the membrane fraction; twenty-four hour treatment resulted in the downregulation of these isoforms. In contrast, dPPA was found to be a potent activator of PKC-epsilon alone and exhibited weaker effects on alpha and theta. These data suggest that PKC isoforms beta, delta, eta, and zeta, which appear not to be activated by either phorbol ester, are unlikely to be primarily involved in megakaryocytic maturation in response to these agents. The isoforms that are translocated by both phorbol esters-PKC isoforms alpha and theta, and particularly epsilon-are more likely to transduce the signals that stimulate Dami cell differentiation.
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PMID:Expression and activation of protein kinase C isoforms in a human megakaryocytic cell line. 895 Feb 33

The detailed mechanisms underlying long-term potentiation (LTP) are not known. In hippocampal CA1, translocation of protein kinase C (PKC) activity from cytosol to membrane and subsequent phosphorylation of growth associated protein (GAP)-43 have been demonstrated to be critical events for the maintenance phase of LTP. LTP in mossy fiber (MF)-CA3 pathway and the Schaffer collateral/commissural (SC)-CA1 pathway differ in a number of ways: SC-CA1 LTP depends on NMDA receptors while MF-CA3 LTP does not, and SC-CA1 LTP is primarily postsynaptic while MF-CA3 LTP is primarily presynaptic. The role of PKC in MF-CA3 LTP has not been studied. We investigated the role of PKC in CA3 and show that PKC inhibitors prevent LTP, but that PKC activators produce a reversible synaptic potentiation, indicating that PKC activation is an essential but not sufficient component of LTP in CA3. Then using antibodies against specific PKC isozymes we have determined the membrane vs. cytosolic distribution of various PKC isozymes in slices subjected to low or tetanic stimulation, or perfused with phorbol esters (PDAc). Compared with control, LTP and PDAc slices show greater PKC-alpha and -epsilon immunoreactivity in the membrane fraction, indicating that both LTP and phorbol ester treatment induce translocation of PKC-alpha and -epsilon from cytosol to membrane. However, with PKC-beta and PKC-gamma the only detectable translocation from cytosol to membrane was in the phorbol ester-treated slices. Thus, while phorbol ester treatment causes translocation of PKC-alpha, -beta, -gamma and -epsilon, the only detectable translocation associated with CA3 LTP is that of PKC-alpha and -epsilon.
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PMID:The translocation and involvement of protein kinase C in mossy fiber-CA3 long-term potentiation in hippocampus of the rat brain. 895 49

The function of the c-Raf-1 zinc finger domain in the activation of the Raf kinase was examined by the creation of variant zinc finger structures. Mutation of Raf Cys 165 and Cys 168 to Ser strongly inhibits the Ras-dependent activation of c-Raf-1 by epidermal growth factor (EGF). Deletion of the Raf zinc finger and replacement with a homologous zinc finger from protein kinase C gamma (PKC gamma) (to give gamma/Raf) also abrogates EGF-induced activation but enables a vigorous phorbol myristate acetate (PMA)-induced activation. PMA activation of gamma/Raf does not require endogenous Ras or PKCs and probably occurs through a PMA-induced recruitment of gamma/Raf to the plasma membrane. The impaired ability of EGF to activate the Raf zinc finger variants in situ is attributable, at least in part, to a major decrement in their binding to Ras-GTP; both Raf zinc finger variants exhibit decreased association with Ras (V12) in situ upon coexpression in COS cells, as well as diminished binding in vitro to immobilized, processed COS recombinant Ras(V12)-GTP. In contrast, Raf binding to unprocessed COS or prokaryotic recombinant Ras-GTP is unaffected by Raf zinc finger mutation. Thus, the Raf zinc finger contributes an important component to the overall binding to Ras-GTP in situ, through an interaction between the zinc finger and an epitope on Ras, distinct from the effector loop, that is present only on prenylated Ras.
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PMID:An intact Raf zinc finger is required for optimal binding to processed Ras and for ras-dependent Raf activation in situ. 897 84

We showed previously that associative learning induced a twofold increase in protein kinase C gamma-immunoreactivity (PKC gamma-ir) in rabbit CA1 pyramidal neurons, whereas subicular neurons remained unchanged. Here, we investigated the effects of associative learning on PKC-positive astrocytes by determining their numerical density in the CA1 region and the subiculum of naive, pseudoconditioned and trace eyeblink conditioned rabbits. Associative learning induced a 70-80% reduction in the number of PKC beta 2- and gamma-positive astrocytes in the CA1 region, but not in the subiculum. No changes were found in the number of PKC alpha- or beta 1-positive astrocytes in either hippocampal subregion. These results suggest a conditioning-specific downregulation of PKC beta 2 and gamma in a subset of astrocytes in a brain region where a simultaneous alteration in neuronal PKC gamma was evident.
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PMID:Associative learning down-regulates PKC beta 2- and gamma-immunoreactivity in astrocytes. 898 61

1. The aim of this study was to investigate protein kinase C (PKC) gene expression in spontaneously hypertensive rats (SHR). 2. Using the PKC oligodeoxyribonucleotide probes (gamma, epsilon), we detected PKC isoforms gene expression in the heart and brain of 4 and 20 week old SHR with those of age-matched Wistar-Kyoto (WKY) rats by northern blot analysis. 3. In the cerebral cortex, there were significantly increased levels of expression of the Ca2+-dependent isoform PKC-gamma in 4 and 20 weeks SHR compared with that of WKY, while Ca2+ -independent isoform PKC-epsilon did not differ between SHR and WKY. 4. In ventricular myocytes, there was a significant expression of the Ca2+-independent isoform PKC-epsilon in 4 and 20 week old SHR compared with that of WKY, while Ca2+ -dependent isoform PKC-gamma could not be detected in the same extracts of SHR or WKY. 5. We conclude that both of the Ca2+ -dependent and Ca2+ -independent PKC could be involved in the pathogenesis of SHR. Ca2+ -dependent PKC-gamma may be mainly involved in the modulation of blood pressure in the level of the central nervous system, while Ca2+ -independent PKC-epsilon could be related to the genetic myocardial hypertrophy.
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PMID:Expression of protein kinase C gene in the brain and heart of spontaneously hypertensive rats. 907 58

Recent reports have suggested the existence of a causal relationship between impaired regression of multiple climbing fibre innervation and impaired motor coordination in protein kinase C gamma subunit (PKC gamma) mutant mice. In the present patch-clamp study, performed in thin cerebellar slices prepared from adult mutant mice deficient in metabotropic glutamate receptors of the mGluR1 subtype, only 15% of Purkinje cells remained multiply innervated by climbing fibres, but motor coordination was largely impaired in these animals. The present results do not preclude the existence of a causal relationship between impairement of regression of multiple innervation during development and improper motor coordination in the adult.
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PMID:Incomplete regression of multiple climbing fibre innervation of cerebellar Purkinje cells in mGLuR1 mutant mice. 908 Apr 50

The protein kinase C family of enzymes is composed of at least ten different isoforms that display a variety of distinct biochemical specificities. Many of these isoforms are highly expressed in brain, and some show regional specificity in their distribution, suggesting that they may serve specific functions. By using immunocytochemistry to localize the betaI, betaII, gamma, or delta isoforms of protein kinase C in the central vestibular system of the adult rat, we found the vestibular ganglion and its peripheral and central processes of the eighth nerve to be heavily labeled with protein kinase C betaI immunoreactivity. Labeled axons and terminals were also found in all four vestibular nuclei. Some neurons of the vestibular ganglion were weakly stained with the antibody to protein kinase C betaII, as were scattered axons in the eighth nerve, and scattered axons and terminals were found in all four vestibular nuclei among weakly labeled neurons. A few axons in the vestibular portion of the eighth nerve were labeled with protein kinase C gamma immunoreactivity, and neurons of the spinal, lateral, and superior vestibular nuclei were heavily decorated with synapses, presumably derived from Purkinje neurons, which were also strongly immunoreactive. Neurons of the medial vestibular nucleus were not as heavily innervated. With the antibody to protein kinase C delta, we found scattered, weakly immunoreactive neurons in the vestibular portion of the eighth nerve. Myelinated fiber bundles of the spinal vestibular nucleus contained moderate numbers of labeled axons, and the other vestibular nuclei were well innervated by protein kinase C delta axons and terminals. Most of these probably derive from Purkinje cells, which were labeled in longitudinal bands interspersed with bands of labeled basket cells. These data suggest that particular protein kinase C isoforms play specific roles in vestibular and cerebellar function.
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PMID:Protein kinase C in central vestibular, cerebellar, and precerebellar pathways of the rat. 926 15

Classical protein kinase C (PKC) family members are activated by the binding of various ligands to one of several cysteine-rich domains of the enzyme. The natural agonist, diacylglycerol (DAG), and the natural product superagonist, phorbol dibutyrate (PDB), activate the enzyme to produce wide-ranging physiological effects. The second cysteine-rich (Cys2) domain of rat brain PKC-gamma was expressed and labeled with 15N and 13C, and the solution structure was determined to high resolution using multidimensional heteronuclear NMR methods. The phorbol binding site was identified by titrating this domain with phorbol-12,13-dibutyrate (PDB) in the presence of organic cosolvents. Titrations of this domain with lipid micelles, in the absence and presence of phorbols, indicate selective broadening of some resonances. The observed behavior indicates conformational exchange between bound and free states upon protein-micelle interaction. The data also suggest that half of the domain, including the phorbol site and one of the zinc sites, is capable of inserting into membranes.
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PMID:NMR structure of a protein kinase C-gamma phorbol-binding domain and study of protein-lipid micelle interactions. 927 1


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