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)

The RL cell line is an EBV-negative, surface IgM, IgD-positive B lymphoma line, which is significantly growth arrested in the presence of acrylamide-linked antibodies to the surface IgM receptor. We demonstrate here that activation of protein kinase C (PKC) with PMA abrogates anti-IgM-induced phosphoinositide turnover and Ca2+ mobilization; however, growth inhibition is not affected. In addition, inhibitors of PKC are unable to reverse the anti-IgM-mediated growth inhibition. Two-dimensional gel electrophoresis reveals a different pattern of protein phosphorylation after treatment of RL with PMA or anti-IgM. These data strongly suggest that anti-IgM-induced growth inhibition does not rely on phospholipase C-mediated phosphoinositide turnover, Ca2+ mobilization, or PKC activation. On the other hand, the phosphatase inhibitor orthovanadate results in an augmentation of proteins phosphorylated on tyrosine and the growth inhibition which follows anti-IgM treatment. Furthermore, protein tyrosine kinase inhibitors, genistein and herbimycin A, are able to reverse the anti-IgM-induced inhibition of growth. These data demonstrate that multiple signaling pathways are activated by the interaction of anti-IgM with its ligand, and suggest that tyrosine kinase activation is a critical component of the inhibitory response.
 ...
PMID:Anti-IgM-mediated growth inhibition of a human B lymphoma cell line is independent of phosphatidylinositol turnover and protein kinase C activation and involves tyrosine phosphorylation. 191 71

Phosphorylation of various proteins and the activities of specific kinases were studied in tumour cells after hyperthermia. P388 lymphoid tumour cells were treated at 40-45 degrees C for 1 h in vitro. Immediately after heat treatment, particulate and cytosol cell fractions were isolated, phosphorylated proteins separated and various kinase activities were measured. Hyperthermic treatment of the cells caused a significant decrease in protein kinase C activity while the activity of calcium-ion and phospholipid-independent protein kinases increased. Phosphorylation of cytosol proteins of 120, 80, 33, 25 and 14 kDa increased significantly after hyperthermia, and protein kinase C selectively phosphorylated the last three of these proteins. The phosphorylation of three heat shock proteins (44, 70 and 85 kDa) was not changed after hyperthermic treatment. Four tyrosine kinase activities were separated. The protein tyrosine kinase activity decreased to one-tenth of the control value after 45 degrees C for 1 h hyperthermia. The changes in kinase activities and protein phosphorylation induced by hyperthermia proved to be temperature- and time-dependent.
 ...
PMID:Protein phosphorylation and kinase activities in tumour cells after hyperthermia. 197 24

We examined the expression of the proto-oncogene c-fos and the early growth response gene, Egr-1, in Rat 1 fibroblasts expressing high levels of normal or mutated human insulin receptors (McClain, D. A., Maegawa, H., Lee, J., Dull, T. J., Ullrich, A., and Olefsky, J. M. (1987) J. Biol. Chem. 262, 14663-14671). In cells expressing large numbers of normal human insulin receptors (HIRc-B cells), insulin (greater than or equal to 0.7 nM) stimulated the rapid accumulation of mRNAs for both genes. This response was blunted, but not lost, in cells expressing large numbers of human insulin receptors missing 43 amino acids at the carboxyl terminus of the beta-subunit. In contrast, the insulin response was completely absent in cells expressing large numbers of receptors that contained a mutation at the ATP-binding site that destroyed intrinsic protein tyrosine kinase activity (A/K 1018-B cells). This mutation also suppressed the modest transcriptional response to insulin that occurred in the parental Rat 1 cells. The transcriptional response to serum was normal in the A/K 1018-B cells, even after protein kinase C depletion; however, the response to insulin-like growth factor I was essentially lost. These studies suggest that overexpression of a kinase-deficient insulin receptor can suppress the transcriptional response to both insulin and insulin-like growth factor I that is ordinarily transduced through endogenous insulin and insulin-like growth factor I receptors, respectively. Competition for shared substrates of these related receptor kinases is a potential mechanism for this effect.
 ...
PMID:Cellular expression of mutant insulin receptors interferes with the rapid transcriptional response to both insulin and insulin-like growth factor I. 198 10

The T cell antigen receptor (TCR) is a multisubunit surface molecule on T cells which recognizes foreign antigens. In addition to the clone-specific alpha beta or gamma delta heterodimer antigen recognition element, each TCR has five invariant chains--the CD3-gamma, -delta, and -epsilon chains and a zeta zeta or zeta eta disulfide dimer. Receptor assembly and surface expression requires the presence of all chains except eta. Targetting of partial complexes, however, is determined differently by specific chains with the zeta chain in murine T cells providing safe transport of assembled pentamers from the Golgi complex to the cell surface. TCR signalling involves activation of two kinase pathways--protein kinase C and a non-receptor protein tyrosine kinase. zeta eta-containing TCRs couple preferentially to the PKC pathway by mediating phosphoinositide hydrolysis. We have evidence that the activated protein tyrosine kinase may be fyn, a member of the src family. While specific signalling roles for all invariant chains are not yet defined, we have implicated the zeta chain as uniquely coupling TCR antigen engagement to distal IL-2 signalling, perhaps via activation of the tyrosine kinase pathway.
 ...
PMID:The structure and signalling functions of the invariant T cell receptor components. 215 1

Chronic, oral administration of aluminum to rats increases the in vivo concentration of cyclic AMP and the phosphorylation of microtubule-associated protein-2 (MAP-2) and the 200 kD neurofilament subunit (15,16). In the present study, the effect of this treatment on endogenous protein phosphorylation in soluble and particulate fractions prepared from cerebral cortices was examined. Chronic aluminum treatment significantly elevated the basal and cyclic AMP-dependent phosphorylation of 11-12 endogenous proteins in the soluble fraction prepared from cerebral cortices. Endogenous protein phosphorylation in the soluble fraction occurring in the presence of Ca++ alone or Ca++, phorbol 12-myristate 13-acetate and phosphatidylserine was not significantly altered by aluminum treatment. In the particulate fraction the phosphorylation of several proteins was significantly decreased by aluminum administration; however, the phosphorylation of the majority of protein substrates remained unaltered. Aluminum treatment did not alter the activities of cyclic AMP-dependent protein kinase or protein tyrosine kinase in the soluble and particulate fractions. The activity of Ca++/phospholipid-dependent protein kinase (protein kinase C) was increased in the particulate fraction of aluminum-fed rats. These results clearly demonstrate that specific effects on protein phosphorylation and protein kinase activities result from in vivo aluminum administration.
 ...
PMID:Oral aluminum alters in vitro protein phosphorylation and kinase activities in rat brain. 216 94

Epidermal growth factor (EGF)-induced receptor dimerization may provide a mechanism for activation of the receptor protein tyrosine kinase and for initiation of post-receptor signalling pathways. We have examined whether second messengers and agents that modulate EGF receptor function act at the level of receptor dimerization. Both the Ca2+ ionophore ionomycin and the tumour promotor tetradecanoylphorbol acetate (TPA), added shortly before EGF, inhibit EGF receptor protein tyrosine kinase activity in intact cells. In permeabilized cells, elevation of Ca2+ similarly inhibits EGF receptor function. The inhibitory effect of Ca2+, unlike that of TPA, appears not to be dependent on protein kinase C activity. Neither ionomycin nor phorbol ester affects EGF-induced receptor dimerization, as shown by cross-linking and immunoblotting techniques, although the phosphotyrosine content of both monomeric and dimeric receptors is strongly decreased. Furthermore, we show that EGF receptor dimerization is not affected by increases in cyclic AMP or intracellular pH, nor by changes in transmembrane potential, medium osmolarity or the glycosylation state of the receptor. These result suggest that modulation of EGF receptor function occurs at a step other than receptor dimerization.
 ...
PMID:Second messenger modulation of epidermal growth factor receptor function does not occur at the level of receptor dimerization. 217 99

Several growth factors and mitogens have been shown to activate the proto-oncogene product Raf-1 protein kinase in murine fibroblasts, apparently through a direct agonist-stimulated tyrosine phosphorylation of the Raf-1 protein. We investigated the possibility that insulin could also activate the Raf-1 kinase, since its receptor also contains an intrinsic insulin-activated protein tyrosine kinase activity. In several cell lines expressing relatively large numbers of insulin receptors, insulin rapidly stimulated the phosphorylation of immunoreactive Raf-1 protein. In H35 cells, a line of well differentiated rat hepatoma cells, the effect of insulin was maximal by 6 min and at 7 nM insulin and occurred normally in cells virtually completely depleted of protein kinase C activity. The insulin-stimulated increase in Raf-1 protein phosphorylation occurred concurrently with a 3-fold increase in Raf-1 protein kinase activity. However, phosphoamino acid analysis showed that only phosphoserine and a trace of phosphothreonine were present in the Raf-1 protein after insulin stimulation of the cells. This was true even when investigated at shorter times (4 min) after insulin stimulation and despite the use of phosphotyrosine phosphatase inhibitors. We conclude that insulin can rapidly activate the Raf-1 kinase in some insulin-sensitive cell types but that this activation probably occurs through a mechanism distinct from direct phosphorylation of the Raf-1 protein by the insulin receptor protein tyrosine kinase.
 ...
PMID:Insulin activates the Raf-1 protein kinase. 219 71

The growth inhibitory effects of exogenously added retinoic acid (RA) on various cultured human glioma cells was observed to be heterogenous, with an ID50 ranging from 10(-7) M to no response. The protein tyrosine kinase activity of epidermal growth factor receptor (EGF-receptor) appeared to parallel the cell's growth responsiveness to RA. Cells sensitive to RA-induced growth inhibition exhibited a dose-dependent decrease in EGF-receptor activity, whereas RA-resistant cells showed no alterations in EGF-receptor protein tyrosine kinase activity or expression. The modulation of EGF-receptor by RA was further examined with RA-sensitive (LG) and -resistant (NG-1) cell lines. Both cell lines were approximately equal in their ability to bind and internalize epidermal growth factor in the presence or absence of RA. Several independent assays suggested that the inhibition of EGF-receptor activity was independent of protein kinase C modulation as mediated by phorbol myristate acetate. However, alterations in associated glycoconjugates of EGF-receptor were observed among the sensitive cells but not the resistant cells. These results suggest RA-induced growth inhibition in sensitive cells may arise, at least in part, through alterations in EGF-receptor and structure.
 ...
PMID:Inhibition of epidermal growth factor receptor activity by retinoic acid in glioma cells. 230 13

We have studied the insulin-stimulated phosphorylation of proteins in NIH 3T3 cells expressing high numbers of human insulin receptors (HIR 3.5 cells) using the technique of giant two-dimensional gel electrophoresis. In serum-deprived cells, insulin stimulated the phosphorylation of more than 25 proteins; all but two of these were also phosphorylated in response to 15% (v/v) fetal bovine serum, which also stimulated the phosphorylation of additional proteins thought to be direct substrates for protein kinase C. In cells pretreated insulin specifically stimulated the phosphorylation insulin specifically stimulated the phosphorylation of at least 26 predominantly cytosolic proteins, only one of which was observed in insulin-treated cells not exposed to phenylarsine oxide. Serum was without effect in cells pretreated with phenylarsine oxide. In phenylarsine oxide-pretreated cells, phosphoamino acid analysis of 10 of the most highly labeled insulin-stimulated phosphoproteins showed that all 10 were labeled predominantly or exclusively on tyrosine residues. The phosphorylation of several of these could be stimulated in vitro by the addition of insulin to a detergent extract of cells in the presence of Mn2+ and ATP. In general, the insulin-stimulated phosphorylations observed in the presence of phenylarsine oxide were more rapid than those observed in its absence. Finally, a variety of other growth factors and mitogens did not stimulate any of the insulin-stimulated phosphorylations in the presence of phenylarsine oxide. Thus, the use of this inhibitor apparently unmasked a number of novel insulin-specific protein phosphorylations that were ordinarily undetectable. We suggest that at least some of these proteins may be direct substrates for the insulin receptor protein tyrosine kinase and may play significant roles in insulin action.
 ...
PMID:Insulin-stimulated protein tyrosine phosphorylation in intact cells evaluated by giant two-dimensional gel electrophoresis. 247 42

We have characterized a 68 kDa lipocortin from human placenta that was identified as a covalently linked homodimer of lipocortin-1 by peptide mapping and sequence analysis. The site of cross-linking was localized within the 3 kDa N-terminal tail region, an exposed domain that contains the phosphorylation sites for protein tyrosine kinase and protein kinase C and is sensitive to proteolysis. Sequence analysis of the corresponding peptide revealed that glutamine-18 was modified, suggesting that the cross-link may be generated by a transglutaminase. By incubating lipocortin-1 with placental membranes and with labelled glycine ethyl ester we observed a Ca2+-dependent labelling of lipocortin-1 within the tail region, supporting this notion. Like lipocortin-1, the dimer inhibits phospholipase Ad2 activity, is a substrate for the epidermal-growth-factor (EGF) receptor/kinase, and display Ca2+-dependent binding to phosphatidylserine-containing vesicles. In preparations from human placenta the dimer is particularly abundant, accounting for approx. 20% of the lipocortin-1.
 ...
PMID:A dimeric form of lipocortin-1 in human placenta. 253 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>