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)

Protein kinase C (PKC) consists of a family of lipid-regulated enzymes which play a pivotal role in signal transduction. Studies with the cell line R6-PKC3, a derivative of R6 rat fibroblasts that overexpresses PKC beta 1, provide direct evidence that this isoform of PKC influences cell morphology, growth control, the production of an autocrine growth factor, and the action of an activated H-ras oncogene. Analysis of 32P-labelled phosphoproteins indicates that R6-PKC cells display increased phosphorylation of a 80/87 kDa protein (designated MARCKS), and after treatment with TPA they display a dramatic prolongation in the phosphorylation and in the cytosolic accumulation of this protein. These alterations in MARCKS may be responsible, at least in part, for the altered growth properties of R6-PKC3 cells. We have also examined the expression of endogenous isoforms of PKC in R6 cells and oncogene-transformed derivatives. Normal R6 cells express four isoforms of PKC, cPKC alpha, nPKC epsilon, nPKC delta, and nPKC zeta; nPKC delta and nPKC epsilon are the most abundant. nPKC epsilon and nPKC delta have an unusual distribution since 60-80% is membrane-bound. In response to TPA, the cytosolic levels of all four PKC isozymes were recruited to the membrane fraction. Prolonged treatment of R6 cells with TPA caused total loss of cPKC alpha, nPKC delta and nPKC zeta but only a 60% reduction in nPKC epsilon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The roles of specific isoforms of protein kinase C in growth control and human colon cancer. 184 47

The biochemical effects of the human H-, N- and K-ras oncogenes were studied. We analysed the induction of c-fos mRNA and protein by the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in exponentially growing NIH3T3 fibroblasts transformed by transfection with ras oncogenes. We found that H-ras has the unique ability to inhibit c-fos induction by TPA. In contrast, normal c-fos expression was induced by TPA in fibroblasts transformed by N- or K-ras or by the ras-unrelated oncogenes dbl and trk. The inhibition of c-fos induction by H-ras was not due to alteration in the binding of TPA to the transformed cells or to the selection of idiosyncratic clones. These results provide clear evidence that H-ras is functionally different from K- or N-ras.
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PMID:Human Harvey-ras is biochemically different from Kirsten- or N-ras. 190 5

Insulin treatment of fibroblasts overexpressing the insulin receptor causes a rapid accumulation of the GTP-bound form of p21ras. We have studied the involvement of protein kinase C (PKC) in, and the effect of phenylarsine oxide (PAO), a putative inhibitor of tyrosine phosphatase activity on, this process. Activation of p21ras was not observed when the cells were stimulated with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and pretreatment with TPA for 16 h, sufficient to down-regulate PKC activity, did not abolish p21ras activation by insulin. These results show that PKC is not involved in the insulin-induced activation of p21ras. Pretreatment of the cells with PAO for 5 min completely blocked insulin-induced p21ras activation. Addition of 2,3-dimercaptopropanol prevented this inhibition by PAO. Also, addition of PAO after insulin stimulation could reverse the activation of p21ras. Since PAO did not affect overall phosphorylation of the insulin receptor beta-chain, we conclude that a PAO-sensitive protein is involved in the induction of p21ras activation by insulin.
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PMID:Insulin-induced p21ras activation does not require protein kinase C, but a protein sensitive to phenylarsine oxide. 193 60

Synergy between ionomycin and sn-1,2-dioctanoylglycerol (diC8) was shown at the level of lymphokine gene transcription. Transcriptional activation of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and the protooncogene H-ras was accomplished by signaling highly purified normal human resting T-lymphocytes (T-cells) with diC8, a physiologic regulator of protein kinase C, and the calcium ionophore, ionomycin. Northern blot analysis of mRNA for early T-cell activation genes demonstrated the synergism between diC8 and ionomycin at the gene induction level. To amplify very low levels of IL-2 mRNA, sequential reverse transcription and polymerase chain reaction (RT-PCR) of T cell mRNA were used to demonstrate the capacity of the calcium signal (ionomycin) to promote low-level IL-2 transcription in normal human T-cells without additional signals. Cyclosporine (CsA) prevented diC8 and ionomycin-induced expression of IL-2, IFN-gamma, and H-ras genes. The completeness of its inhibitory effect was evident by the absence of IL-2 transcripts in CsA-treated cultures screened by the RT-PCR technique. CsA also prevented IL-2 and IFN-gamma gene expression in accessory cell-depleted T-cells stimulated by cross-linking the CD2 and CD3 antigens on the cell surface. Our observations demonstrate that a physiologic regulator of PKC, diC8, and cell surface crosslinking of the CD2 and CD3 antigen, promote gene expression in normal human quiescent T-cells independently of accessory cells, and that CsA prevents gene expression via a direct effect on T-cells.
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PMID:Physiologic signaling in normal human T-cells: mRNA phenotyping by northern blot analysis and reverse transcription-polymerase chain reaction. 197 31

Oncogenic forms of p21ras are found in a wide range of human tumors. However, the mechanism by which p21ras transforms remains obscure. Genetic evidence has identified a domain of p21ras that is involved with interaction with an effector molecule required for transformation. Two proteins, GAP and the tumor suppressor NF1, interact with p21ras in this region but it is an unresolved puzzle whether either of these is the an unresolved puzzle whether either of these is the effector. After interaction with an effector, two downstream events--activation of protein kinase C and another pathway--are necessary for induction of DNA synthesis by oncogenic p21ras; however, morphological transformation does not require activation of protein kinase C.
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PMID:How does p21ras transform cells? 203 Dec 88

Phosphorylation in normal and transformed NIH3T3 cells of the 80K protein, a specific substrate for protein kinase C, was compared by means of two-dimensional gel analysis. We obtained evidence that NIH3T3 cells transformed by the c-raf or H-ras oncogene maintained a decreased level of phosphorylation of the 80K protein, with or without phorbol ester (TPA)-stimulation, at all concentrations of serum tested while normal NIH3T3 cells maintained an elevated level of phosphorylation of the 80K protein. Furthermore, NIH3T3 cells transformed by N-ras, K-ras, src, mos or polyoma middle T antigen exhibited a decreased level of phosphorylation of the 80K protein. These events were confirmed by an analysis of a hormone-inducible H-ras transformant. Thus, phosphorylation of the 80K protein is inversely correlated with cellular transformation.
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PMID:Transformation-specific decrease of phosphorylation of 80K protein, a substrate of protein kinase C, in NIH3T3 cells. 211 92

Epstein-Barr virus (EBV) infects human B lymphocytes and efficiently transforms them into immortalized lymphoblasts. EBV-determined nuclear antigen (EBNA) and EBV latent infection membrane protein (LMP) are expressed in latently infected, growth-transformed lymphoblasts. To elucidate the functions of EBNA and LMP, clones of cells were established that stably expressed EBNA-1, EBNA-2, EBNA-3A, EBNA-leader protein (EBNA-Lp) or LMP, using gene transfer technique and the growth characteristics of the transfectants were examined. The expression of EBNA-1, EBNA-2,EBNA-3A,EBNA-Lp or LMP caused shortening of doubling time, increased saturation cell density, reduced serum dependence, anchorage-independent growth in semisolid agar and activation of c-myc. Furthermore, the expression of LMP in NIH/3T3 cells led to tumorigenicity in nude mice, enhanced expression of H-ras and increased production of diacylglycerol, which might activate protein kinase C. B cell line, BJAB, EBNA-1 was responsible for expression of c-fgr mRNA and EBNA -2 specifically induced expression of B-cell activation antigens, including CD21 (CR2) and CD23 (Fc epsilon receptor). These results indicate that EBNA and LMP play an important role in EBV-induced growth transformation. It is possible that EBNA-1 and EBNA-2 are directly involved in the early process of immortalization. It is also possible that LMP could contribute to tumorigenic alteration of immortalized cells. The proliferation of the EBNA or LMP-expressing cells was markedly enhanced by phorbol ester. By contrast phorbol ester had no effect on the proliferation of nonexpressing control cells. The phorbol ester enhancement of EBV-induced growth transformation is likely to be mediated by EBNA and LMP.
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PMID:[Studies on transforming functions of Epstein-Barr virus-specific proteins]. 217 30

1. The ability of bombesin or platelet-derived growth factor (PDGF) to stimulate Ca2+ inflow (assessed by measuring changes in the intracellular free Ca2+ concentration in cells loaded with fura-2) in NIH-3T3 cells transformed with the EJ/T24-Ha-ras-1 oncogene is inhibited when compared with the action of the agonists on wild-type cells. 2. The effects of transformation with the ras oncogene are associated with complete inhibition of the ability of bombesin to release Ca2+ from intracellular stores, a substantial decrease in the number of bombesin receptors, no change in the ability of foetal calf serum or ionomycin to release Ca2+ from intracellular stores and the activation of protein kinase C. 3. The effects of transformation with the H-ras oncogene on the ability of bombesin or PDGF to stimulate Ca2+ inflow were mimicked by a 30 min exposure of wild-type cells to phorbol dibutyrate. This action of phorbol dibutyrate was completely blocked by prior treatment of wild-type cells for 24 h with the phorbol ester. 4. It is concluded that one of the actions of the H-ras oncogene in fibroblasts is to inhibit agonist-stimulated Ca2+ inflow by a mechanism which involves the activation of protein kinase C.
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PMID:NIH-3T3 cells transformed with a ras oncogene exhibit a protein kinase C-mediated inhibition of agonist-stimulated Ca2+ inflow. 217 57

External signals that control the activity of proteins encoded by the ras proto-oncogenes have not previously been characterized. It is now shown that stimulation of the antigen receptor of T lymphocytes causes a rapid activation of p21ras. The mechanism seems to involve a decrease in the activity of GAP, the GTPase-activating protein, on stimulation of protein kinase C. In lymphocytes, p21ras may therefore be an important mediator of the action of protein kinase C.
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PMID:Stimulation of p21ras upon T-cell activation. 220 20

Rat embryo fibroblasts and liver epithelial cell lines normally express two isoforms of protein kinase C (PKC), PKC alpha and PKC epsilon. Derivatives of these cells transformed by an activated human c-H-ras oncogene display a several-fold increase in expression of PKC alpha and a concomitant decrease in PKC epsilon, at both the protein and mRNA levels. Similar changes are seen when the transformed phenotype is induced by Zn2+ in cells carrying the activated ras oncogene under the control of a metallothionein promoter. Studies using cell lines that express very high levels of PKC beta 1, studies using a specific inhibitor of PKC (CGP 41251), and studies in which PKC activity is down-regulated by treatment with a phorbol ester tumor promoter provide evidence that the effects of the ras oncogene on the expression of PKC alpha and PKC epsilon are mediated mainly through a PKC-independent pathway. The present results provide the first evidence that transformation of cells by an oncogene can alter the relative expression of specific isoforms of PKC. It is possible that these changes contribute to the malignant phenotype of these cells.
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PMID:Transformation by a ras oncogene causes increased expression of protein kinase C-alpha and decreased expression of protein kinase C-epsilon. 228 79


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