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)

Stimulation of the T cell receptor-CD3 complex activates multiple signal transduction pathways, including serine/threonine and tyrosine protein kinases. Stimulation of the human T cell line Jurkat via the T cell receptor-CD3 complex with anti-CD3 monoclonal antibody or incubation with the tumor promoter phorbol 12-myristate 13-acetate caused increases in S6 kinase and microtubule-associated protein 2 (MAP) kinase activities. An S6 kinase activity that was able to phosphorylate exogenous 40S ribosomal S6 protein was recovered in immunoprecipitates obtained using a 90-kDa ribosomal S6 kinase-specific antiserum and thus represents activation of a member of the 90-kDa ribosomal S6 kinase family. Stimulation of the S6 kinase activity correlated with an increase in a kinase activity able to phosphorylate exogenous 90-kDa ribosomal S6 kinase (rsk) attributed to a MAP kinase activity. These increases in S6 and MAP kinase activities further correlated with the appearance of a 42-kDa phosphoprotein detected by anti-phosphotyrosine immunoblotting. However, while the tyrosine phosphorylation of the 42-kDa protein and the MAP kinase activity are dependent on protein kinase C activity, residual S6 kinase activity can be detected following protein kinase C depletion and subsequent anti-CD3 stimulation. Thus, T cell activation through the T cell receptor-CD3 complex results in activation of a member of the 90-kDa S6 kinase family which correlates with, but can be independent of, MAP kinase activation.
 ...
PMID:T cell receptor activation of a ribosomal S6 kinase activity. 153 81

Synthetic peptide substrates specific for cAMP-dependent protein kinase, protein kinase C, ribosomal S6 kinase, and Ca2+/calmodulin-dependent protein kinases were used to monitor regulation of these protein kinases in digitonin-permeabilized PC12 cells following treatment with nerve growth factor (NGF) and epidermal growth factor (EGF). cAMP-dependent protein kinase was not activated by NGF and EGF. In addition, neither the Ca2+/calmodulin-dependent nor -independent activity of a protein kinase similar to Ca2+/calmodulin kinase II was affected by growth factor treatment. However, protein kinase C was rapidly and transiently activated and ribosomal S6 kinase activity was persistently elevated. Maximal protein kinase C activity was observed after 2 to 5 min of treatment and, subsequently, returned to control levels within 30 to 40 min. In contrast, S6 kinase activity was maximal within 15 min of NGF and EGF addition and was stably maintained for at least 24 hr. In addition to protein kinase C and S6 kinase, NGF and EGF regulated a protein kinase that was maximally elevated after 15 to 30 min and returned to control levels within 3 to 5 hr. This kinase (approximately 100 kDa) failed to bind to a calmodulin affinity column and eluted from a cation exchange column as a single major species that was distinct from S6 kinase activity, which eluted as multiple peaks. The findings indicate that at least three protein kinases are rapidly activated in PC12 cells following treatment with NGF and EGF. The distinct durations of activation of each kinase implicates significantly different roles for each in growth factor signalling in PC12 cells.
 ...
PMID:Detection of nerve growth factor and epidermal growth factor-regulated protein kinases in PC12 cells with synthetic peptide substrates. 278 35

We have used a permeabilized cell assay and a synthetic peptide substrate (KRTLRR) to specifically monitor the activity of protein kinase C in PC12 cells preincubated with nerve growth factor (NGF), epidermal growth factor (EGF), or phorbol esters. Pretreatment of PC12 cells with 1 microM 12-O-tetradecanoylphorbol 13-acetate or 1 microM phorbol dibutyrate stimulated the rate of KRTLRR peptide phosphorylation 4.8- and 2.6-fold, respectively. Furthermore, pretreatment of cells with NGF or EGF transiently increased the KRTLRR peptide kinase activity. Peak stimulations of KRTLRR peptide kinase (1.3-2-fold) were observed after 1-5 min of growth factor treatment and returned to control levels within 15-20 min. The KRTLRR peptide kinase activity fulfilled two criteria of protein kinase C. A synthetic peptide inhibitor of protein kinase C inhibited both growth factor- and phorbol ester-stimulated KRTLRR peptide kinase activity. In addition, growth factors and phorbol esters failed to stimulate KRTLRR peptide kinase activity in cells rendered protein kinase C-deficient by long-term treatment with 1 microM 12-O-tetradecanoylphorbol 13-acetate. In contrast to the transient activation of protein kinase C, ribosomal S6 kinase, assayed with the synthetic peptide RRLSSLRA, was persistently activated by NGF and EGF. The findings indicate that protein kinase C serves an early and transient role in the molecular actions of NGF and EGF in PC12 cells.
 ...
PMID:Regulation of protein kinase C by nerve growth factor, epidermal growth factor, and phorbol esters in PC12 pheochromocytoma cells. 278 93

Sphingosylphosphorylcholine (SPC) is a potent mitogen for Swiss 3T3 cells, but the signaling mechanisms involved are poorly characterized. Here, we report that addition of SPC induces a rapid and transient activation of p42 mitogen-activated protein kinase (p42MAPK) in these cells. SPC-induced p42MAPK activation peaked at 5 min and was undetectable after 30 min of incubation with SPC. The effect of SPC on p42MAPK activation was comparable to that induced by bombesin and platelet-derived growth factor. As SPC strongly induced phosphorylation of the major protein kinase C (PKC) substrate 80K/MARCKS in either intact or permeabilized cells, we examined whether PKC could be involved in SPC-induced p42MAPK activation. Here, we demonstrate that p42MAPK activation by SPC was dependent on PKC activity as shown by inhibition of PKC with the bisindolymaleimide GF 109203X or down-regulation of PKC by prolonged treatment of Swiss 3T3 cells with phorbol esters. Activation of both PKC and p42MAPK by SPC was markedly inhibited by treatment with pertussis toxin, implicating a G proteins(s) of the Gi/G(o) subfamily in the action of SPC. SPC-induced rapid activation of a downstream target of p42MAPK, p90 ribosomal S6 kinase (p90rsk), also required PKC and a pertussis toxin-sensitive G protein. In addition, SPC-induced mitogenesis was dependent on a Gi protein in Swiss 3T3 cells. SPC also induced p42MAPK activation and DNA synthesis in secondary cultures of mouse embryo fibroblasts through a pertussis toxin-sensitive pathway. As G proteins link many cell surface receptors to effector proteins, we hypothesize, therefore, that SPC could bind to a receptor that mediates at least some of its biological effects in Swiss 3T3 cells and mouse embryo fibroblasts.
 ...
PMID:Sphingosylphosphorylcholine activation of mitogen-activated protein kinase in Swiss 3T3 cells requires protein kinase C and a pertussis toxin-sensitive G protein. 759 45

We report that recombinant glia maturation factor (GMF), a 17-kD brain protein, can be phosphorylated in vitro at the serine residue by protein kinase C (PKC), protein kinase A (PKA), and casein kinase II (CKII), and at the threonine residue by p90 ribosomal S6 kinase (RSK). Endogenous GMF in astrocytes is phosphorylated at the serine (major) and threonine (minor) residues within 15 min after stimulation by phorbol 12-myristate 13-acetate (PMA). Phosphorylation gradually subsides over the next 24 h. The increased phosphorylation is not blocked by the protein synthesis inhibitor cycloheximide and is not accompanied by a rise in the mRNA for GMF and is therefore strictly a posttranslational regulatory phenomenon. The rapid and transient phosphorylation of GMF upon cellular activation suggests an intracellular role, possibly with involvement in signal transduction.
 ...
PMID:Phorbol ester stimulates rapid intracellular phosphorylation of glia maturation factor. 759 24

We have previously shown that stretching cardiac myocytes evokes activation of protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and 90-kD ribosomal S6 kinase (p90rsk). To clarify the signal transduction pathways from external mechanical stress to nuclear gene expression in stretch-induced cardiac hypertrophy, we have elucidated protein kinase cascade of phosphorylation by examining the time course of activation of MAP kinase kinase kinases (MAPKKKs), MAP kinase kinase (MAPKK), MAPKs, and p90rsk in neonatal rat cardiac myocytes. Mechanical stretch transiently increased the activity of MAPKKKs. An increase in MAPKKKs activity was first detected at 1 min and maximal activation was observed at 2 min after stretch. The activity of MAPKK was increased by stretch from 1-2 min, with a peak at 5 min after stretch. In addition, MAPKs and p90rsk were maximally activated at 8 min and at 10 approximately 30 min after stretch, respectively. Raf-1 kinase (Raf-1) and (MAPK/extracellular signal-regulated kinase) kinase kinase (MEKK), both of which have MAPKKK activity, were also activated by stretching cardiac myocytes for 2 min. The angiotensin II receptor antagonist partially suppressed activation of Raf-1 and MAPKs by stretch. The stretch-induced hypertrophic responses such as activation of Raf-1 and MAPKs and an increase in amino acid uptake was partially dependent on PKC, while a PKC inhibitor completely abolished MAPK activation by angiotensin II. These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1 and MEKK, MAPKK, MAPKs and p90rsk, and that angiotensin II, which may be secreted from stretched myocytes, may be partly involved in stretch-induced hypertrophic responses by activating PKC.
 ...
PMID:Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes. 761 16

Transforming growth factor type beta (TGF-beta) is a multifunctional factor that regulates proliferation and differentiation of many cell types. TGF-beta mediates its effects by binding to and activating cell surface receptors that possess serine/threonine kinase activity. However, the intracellular signaling pathways through which TGF-beta receptors act remain largely unknown. Here we show that TGF-beta activates a 78-kDa protein (p78) serine/threonine kinase as evidenced by an in-gel kinase assay. Ligand-induced activation of the kinase was near-maximal 5 min after TGF-beta addition to the cells and occurred exclusively on serine and threonine residues. This kinase is distinct from TGF-beta receptor type II, as well as several cytoplasmic serine/threonine kinases of similar size, including protein kinase C, Raf, mitogen-activated protein kinase kinase kinase, and ribosomal S6 kinase. Indeed, these kinases can be separated almost completely from p78 kinase by immunoprecipitation with specific antibodies. Furthermore, using different cell lines, we demonstrate that p78 kinase is activated only in cells for which TGF-beta can act as a growth inhibitory factor. These data raise the interesting possibility that protein serine/threonine kinases contribute to the intracellular relay of biological signals originating from receptor serine/threonine kinases such as the TGF-beta receptors.
 ...
PMID:Activation of a serine/threonine kinase signaling pathway by transforming growth factor type beta. 861 54

We report that recombinant glia maturation factor (GMF), a 17-kDa brain protein, inhibits the activity of mitogen-activated protein (MAP) kinase in the test tube assay, in particular the ERK1/ERK2 isoforms. A preliminary phosphorylation of GMF by protein kinase A (PKA) dramatically increases its inhibitory effect by over 600-fold (Ki approximately 3 nM), making it the most potent MAP kinase inhibitor ever reported. Immunoprecipitation of GMF from cell extracts using its specific antibody coprecipitates ERK (and vice versa), suggesting the association of the two proteins in the cell. The inhibitory effect of PKA-phosphorylated GMF is specific, as it does not suppress the activity of cdc2 kinase, another proline-directed kinase. Nor does it inhibit MAP kinase kinase (MEK) and MAP kinase-activated protein (MAPKAP) kinase-2, the two enzymes immediately upstream and downstream, respectively, of ERK. Of the other three enzymes that can phosphorylate GMF, only p90 ribosomal S6 kinase (RSK) enhances the inhibitory function of GMF on ERK; protein kinase C (PKC) and casein kinase II (CKII) are without effect. The inhibition of ERK by PKA-phosphorylated GMF suggests that GMF could be one of the mediators of the suppressive effect of the PKA pathway on the MAP kinase pathway. On the other hand, that RSK-phosphorylated GMF also inhibits ERK implies a negative feedback loop in the regulation of MAP kinase activity.
 ...
PMID:In vitro inhibition of MAP kinase (ERK1/ERK2) activity by phosphorylated glia maturation factor (GMF). 863 70

Stimulation of the human interleukin-2 (IL-2)-dependent cell line, Kit225, with IL-2 resulted in the rapid activation of microtubule-associated protein-2 kinase (MAPK), as demonstrated by the tyrosine phosphorylation of p42erk2, the reduced mobility of MAPK in SDS-PAGE gels, and the increased ability of lysates from these cells to phosphorylate myelin basic protein. Measurements of kinase activity in immunoprecipitates of p9O ribosomal S6 kinase (p90rsk) demonstrated that stimulation of this cell line with IL-2 also resulted in the activation of p90rsk. Further, increased MAPK activity occurred following IL-2 stimulation, but not following phorbol 12-myristate 13-acetate (PMA) stimulation in cells depleted of PKC by prolonged treatment with a high concentration of PMA. These results demonstrate that IL-2 stimulation results in the activation of MAPK and p90rsk and that this activation occurs in a PKC-independent manner.
 ...
PMID:Activation of p42erk2 MAPK and p90rsk by IL-2 occurs independently of protein kinase C. 876 55

Oocytes from the Japanese clam Ruditapes philippinarum are naturally blocked at the prophase-I stage of meiosis. Following physiological activation by the neurohormone serotonin (5HT), oocytes undergo germinal vesicle breakdown (GVBD) and reach a second cell cycle arrest in metaphase-I. To identify the kinases activated during meiosis reinitiation, we used a phosphorylation assay following sodium dodecyl sulphate-polyacrylamide gel electrophoresis and in situ renaturation. A soluble 85-kDa serine/threonine kinase (PK85) was highly and consistently activated (up to 17-fold) within 5 minutes following addition of the hormone. This activation occurred 5 to 10 minutes before GVBD and only when 5HT concentration was sufficient to induce meiosis reinitiation. The calcium ionophore A23187 and NH4Cl, two compounds known to induce GVBD by increasing intracellular calcium concentration, also activate PK85. In crude oocyte extracts, the presence of beta-glycerophosphate, NaF, okadaic acid, calyculin A or microcystin, prevented inactivation of PK85, suggesting that it is activated by phosphorylation. Partial purification of PK85 followed by Western blotting showed that this kinase is related to the ribosomal S6 kinase pp90rsk. PK85 phosphorylates the peptides LRRASLG (kemptide) and PLARTLSVAGLPGGK (syntide-2), and to a lesser extent the synthetic polyamino acids poly(R3:S1) while myelin basic protein (MBP), histone III-S, casein, the peptides pEKRPSQRSKYL ((pGlu4)-MBP 4-14), GTFRASIRRLAARRR (NIMA kinase substrate), the protein kinase C (PKC) substrate LRTLRR and the synthetic polyaminoacids poly(R1:P1:T1) were poor substrates. 5HT-induced GVBD and PK85 activation are both inhibited by the phorbol ester 12-myristate 13-acetate (PMA) and this inhibition can be reversed by 5 microM of the bisindolyl-maleimide GF109203X, a potent PKC inhibitor. PMA inhibitory action appears to take place between 5HT binding to its receptor and the intracellular calcium surge since it has no effect on GVBD induced by calcium ionophore A23187 and thapsigargin. Taken together, these results suggest that serotonin-induced activation of PK85 occurs after the intracellular calcium surge in a PKC-independent pathway.
 ...
PMID:Activation of an 85 kDa ribosomal S6 kinase during serotonin-induced oocyte maturation. 884 Jan 88


1 2 3 4 5 6 7 8 Next >>