Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycogen synthase kinase-3 (GSK3) is implicated in the regulation of several physiological processes, including the control of glycogen and protein synthesis by insulin, modulation of the transcription factors AP-1 and CREB, the specification of cell fate in Drosophila and dorsoventral patterning in Xenopus embryos. GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-1 (also known as p90rsk) or p70 ribosomal S6 kinase (p70S6k). Here we show, however, that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3. Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC). Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase.
...
PMID:Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. 852 13

We describe here the cloning and characterization of a cDNA encoding a protein kinase that has high sequence homology to members of the mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MEKK) family; this cDNA is named cATMEKKI (Arabidopsis thaliana MAP kinase or ERK kinase kinase 1). The catalytic domain of the putative ATMEKK1 protein shows approximately 40% identity with the amino acid sequences of the catalytic domains of MAPKKKs (such as Byr2 from Schizosaccharomyces pombe, Ste11 from Saccharomyces cerevisiae, Bck1 from S. cerevisiae, MEKK from mouse, and NPK1 from tobacco). In yeast cells that overexpress ATMEKK1, the protein kinase replaces Ste11 in responding to mating pheromone. In this study, the expression of three protein kinases was examined by Northern blot analyses: ATMEKK1 (structurally related to MAPKKK), ATMPK3 (structurally related to MAPK), and ATPK19 (structurally related to ribosomal S6 kinase). The mRNA levels of these three protein kinases increased markedly and simultaneously in response to touch, cold, and salinity stress. These results suggest that MAP kinase cascades, which are thought to respond to a variety of extracellular signals, are regulated not only at the posttranslational level but also at the transcriptional level in plants and that MAP kinase cascades in plants may function in transducing signals in the presence of environmental stress.
...
PMID:A gene encoding a mitogen-activated protein kinase kinase kinase is induced simultaneously with genes for a mitogen-activated protein kinase and an S6 ribosomal protein kinase by touch, cold, and water stress in Arabidopsis thaliana. 857 Jun 31

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

Although Ras-related small GTPases are believed to control cell proliferation and motility through activation of protein kinase cascades, little is known about the intracellular protein targets of activated kinases. Here we show that the p90 ribosomal S6 kinase 2 (RSK2) phosphorylates actin-binding protein (ABP-280) in intact rat 3Y1 fibroblasts. Growth factors such as fetal calf serum, epidermal growth factor, phorbol 12-myristate 13-acetate, and lysophosphatidic acid stimulate the phosphorylation of serine residues in ABP-280 in quiescent 3Y1 cells. Extracts from 3Y1 cells prepared after stimulation by lysophosphatidic acid, fetal calf serum, and epidermal growth factor retain activated protein kinase activity(s) toward ABP-280 in vitro. ABP kinase activities in lysates from lysophosphatidic acid-stimulated 3Y1 cells can be fractionated by MonoQ anion exchange column chromatography into three peaks having ABP kinase activities. One (ABP kinase peak 1) coelutes with the peak of RSK2 as judged by immunoblotting and S6 peptide kinase assays. Two-dimensional phosphopeptide maps show RSK2 phosphorylated ABP-280 to be phosphorylated at the same site(s) as those stimulated by growth factors in vivo. Incubation of ABP kinase peak 1 fractionated from unstimulated cells with activated ERK2 activates latent ABP kinase activity. These results show RSK2 to phosphorylate ABP-280 in vivo.
...
PMID:Phosphorylation of actin-binding protein 280 by growth factors is mediated by p90 ribosomal protein S6 kinase. 866 82

The effects of the protein tyrosine kinase inhibitor genistein on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity in monkey kidney epithelial CV-1 cells were determined. CV-1 cells were pretreated with genistein for 2 hr before treatment with 100 nM TPA. ODC activity was determined 9 hr after TPA treatment. Genistein inhibited TPA-induced ODC activity at 0.1, 1, 10, 25, 50, 100, 200, and 400 microM by 0%, 0%, 42%, 59%, 62%, 81%, 91%, and 100%, respectively (IC50 = 20 microM). Genistein inhibited TPA-induced mitogen-activated protein kinase (MAPK) tyrosine phosphorylation and the accumulation of steady state levels of ODC mRNA at 400 microM but not at 25 microM. Genistein, at 25 microM, did not alter the TPA-induced phosphorylation of p90 ribosomal S6 kinase but caused a approximately 50% decrease of the TPA-induced phosphorylation of p70 S6 kinase (p70S6K), a protein kinase involved in the control of translational efficiency. Taken together, these data indicate that genistein may inhibit TPA-induced ODC activity at the transcriptional and translational levels through the inhibition of MAPK and p70S6K activation, respectively. The regulation of MAPK and p70S6K may be mediated through different protein tyrosine kinases that have differential sensitivity to genistein.
...
PMID:Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity by genistein, a tyrosine kinase inhibitor. 870 Jan 31

To elucidate the signal transduction pathway from external stimuli to nuclear gene expression in mechanical stress-induced cardiac hypertrophy, we examined the time course of activation of protein kinases such as Raf-1 kinase (Raf-1), mitogen-activated protein kinase kinase (MAPKK), MAP kinases (MAPKs) and 90-kDa ribosomal S6 kinase (p90rsk) in neonatal rat cardiomyocytes. Mechanical stretch rapidly activated Raf-1 and its maximal activation was observed at 1-2 min after stretch. The activity of MAPKK was also increased by stretch, with a peak at 5 min after stretch. In addition, MAPKs and p90rsk were maximally activated at 8 min and at 10-30 min after stretch, respectively. Next, the relationship between mechanical stress-induced hypertrophy and the cardiac renin-angiotensin system was investigated. When the stretch-conditioned culture medium was transferred to the culture dish of non-stretched cardiac myocytes, the medium activated MAPK activity slightly but significantly, and the activation was completely blocked by the type 1 angiotensin II receptor antagonist, CV-11974. However, activation of Raf-1 and MAPKs provoked by stretching cardiomyocytes was only partially suppressed by pretreatment with CV-11974. These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1, MAPKK, MAPKs and p90rsk, and that angiotensin II, which is secreted from stretched myocytes, activates a part of these protein kinases.
...
PMID:Molecular aspects of mechanical stress-induced cardiac hypertrophy. 897 57

We observed previously that glia maturation factor (GMF), a 17-kDa brain protein, is rapidly phosphorylated in astrocytes following stimulation by phorbol ester, and that protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor of extracellular signal-regulated kinase (ERK) and enhancer of p38; both are subfamilies of mitogen-activated protein (MAP) kinase, suggesting GMF as a bifunctional regulator of the MAP kinase cascades. In the current report, we present evidence that PKA-phosphorylated GMF also promotes (11-fold) the catalytic activity of PKA itself, resulting in a positive feedback loop. Furthermore, GMF phosphorylated by protein kinase C (PKC), but not by casein kinase II or p90 ribosomal S6 kinase, also activates PKA (7-fold). It appears that the mutual augmentation of GMF and PKA, and the stimulating effect of PKC, both serve to maximize the influence of PKA on the regulation of MAP kinase cascades by GMF. Using synthetic peptide fragments containing putative phosphorylation sites of GMF, we demonstrate that PKA is capable of phosphorylating threonine 26 and serine 82, whereas PKC, p90 ribosomal S6 kinase, and casein kinase II, can phosphorylate serine 71, threonine 26, and serine 52, respectively. The generation of various phospho-isoforms of GMF may explain its modulation of signal transduction at multiple locations.
...
PMID:Protein kinase A (PKA)- and protein kinase C-phosphorylated glia maturation factor promotes the catalytic activity of PKA. 903 May 86

Physical exercise can cause marked alterations in the structure and function of human skeletal muscle. However, little is known about the specific signaling molecules and pathways that enable exercise to modulate cellular processes in skeletal muscle. The mitogen-activated protein kinase (MAPK) cascade is a major signaling system by which cells transduce extracellular signals into intracellular responses. We tested the hypothesis that a single bout of exercise activates the MAPK signaling pathway. Needle biopsies of vastus lateralis muscle were taken from nine subjects at rest and after 60 min of cycle ergometer exercise. In all subjects, exercise increased MAPK phosphorylation, and the activity of its downstream substrate, the p90 ribosomal S6 kinase 2. Furthermore, exercise increased the activities of the upstream regulators of MAPK, MAP kinase kinase, and Raf-1. When two additional subjects were studied using a one-legged exercise protocol, MAPK phosphorylation and p90 ribosomal S6 kinase 2, MAP kinase kinase 1, and Raf-1 activities were increased only in the exercising leg. These studies demonstrate that exercise activates the MAPK cascade in human skeletal muscle and that this stimulation is primarily a local, tissue-specific phenomenon, rather than a systemic response to exercise. These findings suggest that the MAPK pathway may modulate cellular processes that occur in skeletal muscle in response to exercise.
...
PMID:Exercise stimulates the mitogen-activated protein kinase pathway in human skeletal muscle. 907 33

To understand the insulin-induced activation of 6-phosphofructo-2-kinase (PFK-2) of the bifunctional enzyme PFK-2/fructose-2,6-bisphosphatase in heart, the effect of phosphorylation by protein kinases of the insulin signaling pathways on PFK-2 activity was studied. Purified PFK-2/fructose-2, 6-bisphosphatase from bovine heart is a mixture of two isoforms (Mr 58,000 and 54,000 on SDS-polyacrylamide gels). The Mr 54,000 protein is an alternatively spliced form, lacking phosphorylation sites for protein kinases. Recombinant enzymes corresponding to the Mr 58,000 (BH1) and Mr 54,000 (BH3) forms were expressed and used as substrates for phosphorylation. The recombinant BH1 isoform was phosphorylated by p70 ribosomal S6 kinase (p70(s6k)), mitogen-activated protein kinase-activated protein kinase-1, and protein kinase B (PKB), whereas the recombinant BH3 isoform was a poor substrate for these protein kinases. Treatment with all protein kinases activated PFK-2 in the recombinant BH1 preparation. Phosphorylation of the recombinant BH1 isoform correlated with PFK-2 activation and was reversed by treatment with protein phosphatase 2A. All the protein kinases phosphorylated Ser-466 and Ser-483 in the BH1 isoform, but to different extents: p70(s6k) preferentially phosphorylated Ser-466, whereas mitogen-activated protein kinase-activated protein kinase-1 and PKB phosphorylated Ser-466 and Ser-483 to a similar extent. We propose that PKB is part of the insulin signaling cascade for PFK-2 activation in heart.
...
PMID:Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades. 921 63

Extracellular calcium addition transiently stimulated two S6 peptide kinase activities in isolated rat hepatocytes. Mono Q chromatography revealed that the activities eluting at 0.15 M NaCl and 0.18 M NaCl were stimulated 4-fold and 2-fold, respectively. The kinase stimulated by calcium was a 40000-Mr S6 peptide kinase, as demonstrated by partial purification from whole liver. The protein kinase did not crossreact with antibodies directed against the N- or C-terminal part of p70 ribosomal S6 kinase (p70(S6K)) and the C-terminal part of p90 ribosomal S6 kinase (p90(rsk)). Following digestion of 40000-Mr S6 peptide kinase with trypsin, six peptides were sequenced. There was no similarity with the sequences of p70(S6K) and p90(rsk). Moreover, the obtained sequences could not be identified in the SwissProt or EMBL-genebank databases, suggesting that 40000-Mr S6 peptide kinase probably represents a novel protein kinase.
...
PMID:Identification of a novel Ca2+-stimulated S6-kinase in rat liver. 934 50


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

---