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

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

Eleven Entamoeba histolytica protein-serine/threonine-kinase gene segments were identified using the polymerase chain reaction (PCR) and degenerate oligonucleotide primers to conserved amino acids in subdomains VI and VIII of the catalytic domain of protein-serine/threonine kinases. These ameba gene segments were homologous to myosin light chain kinases, protein kinase C, phosphorylase b kinase, and kinases that regulate glucose repression in yeast and cell growth in mammalian cells. One of these PCR products, which was homologous to the Dictyostelium discoideum protein kinase 2, was used to identify a full-length protein-serine/threonine-kinase gene (Eh rac1) from an E. histolytica genomic library. The open reading frame of Eh rac1 was 409 amino acids long (encoding a 47-kDa protein) and included an amino terminal segment containing 87 mostly charged and polar amino acids and a 322-amino acid carboxyl terminal segment containing the catalytic domain. The catalytic domain of Eh rac1 was homologous to the rac family of protein-serine/threonine-kinases, which are related to cAMP-dependent protein kinases and protein kinase Cs. Southern blots of ameba DNA showed that the Eh rac1 gene was present as a single copy in all strains tested, however pathogenic amebae expressed four times more Eh rac1 mRNAs than did nonpathogenic amebae. These studies suggest that E. histolytica, a primitive unicellular eukaryote, has a complex protein kinase family.
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PMID:Molecular cloning of a rac family protein kinase and identification of a serine/threonine protein kinase gene family of Entamoeba histolytica. 823 9

Enteropathogenic Escherichia coli (EPEC) remain an important cause of infant diarrhoea in many parts of the developing world. Essential for virulence is their ability to adhere to the small intestinal mucosa and produce a striking 'attaching and effacing' (AE) lesion characterised by localised destruction of brush border microvilli, intimate attachment of bacteria to the residual apical enterocyte membrane, often in a cuplike pedestal structure, and formation of a dense plaque of actin (and other) cytoskeletal filaments beneath adherent bacteria. Fluorescence actin staining (FAS test) has turned out to be a useful diagnostic test for the AE lesion and also led to the identification of a chromosomal gene, eae, which is necessary but, by itself, not sufficient to produce the AE lesion. The 94 kDa outer membrane protein encoded by eae may be the adhesin which promotes intimate bacterial attachment. The signal transduction pathway which leads to AE lesion formation has yet to be defined although EPEC induced increased levels in intracellular calcium and phosphorylation of specific cell proteins including myosin light chain suggest that EPEC, by binding to a specific host cell receptor, may be promoting a calcium second message which would a) activate the brush border protein villin to cause microvillar breakdown and b) stimulate protein kinase activity to cause the other cytoskeletal rearrangements.
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PMID:The attaching and effacing virulence property of enteropathogenic Escherichia coli. 834 27

Phosphorylation of myosin light chain kinase by a Ca(2+)-dependent protein kinase increases the concentration of Ca2+/calmodulin required for half-maximal activation. The Ca2+ concentrations required for myosin light chain kinase phosphorylation in permeable smooth muscle are similar to those required for myosin light chain phosphorylation. Both GTP gamma S and carbachol increase the Ca2+ sensitivity of myosin light chain kinase phosphorylation as well as light chain phosphorylation. It is proposed that a similar G-protein mediated mechanism regulates the Ca(2+)-dependent phosphorylation of these two contractile proteins in smooth muscle.
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PMID:GTP gamma S-induced phosphorylation of myosin light chain kinase in smooth muscle. 837 9

Roles of Ca/calmodulin-dependent protein kinase II (Ca/CaM kinase II) and myosin light chain kinase (MLCK) in insulin release from rat pancreatic islets were investigated. Western blotting using polyclonal antibody to Ca/CaM kinase II suggested the presence of this kinase in the pancreatic islets. Extracts of pancreatic islets phosphorylated exogenous myosin light chain, which was inhibited by ML-9, an inhibitor of MLCK. KN-62 and KN-93, inhibitors of Ca/CaM kinase II, and ML-9 at microM concentrations inhibited insulin release stimulated by glucose or high K+. KN-62 and KN-93, but not ML-9, inhibited insulin release increased by glucose and forskolin, an activator of adenylate cyclase. These inhibitors had no effect on insulin release evoked by 12-O-tetradecanoyl phorbol-13-acetate, an activator of Ca(2+)-sensitive, diacylglycerol-dependent protein kinase. These results suggest that Ca/CaM kinase II and MLCK may participate in the control of insulin release.
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PMID:Presence and possible involvement of Ca/calmodulin-dependent protein kinases in insulin release from the rat pancreatic beta cell. 838 89

A Ca(2+)-calmodulin-dependent protein kinase that phosphorylates the regulatory light chain of hepatocyte myosin was purified from rabbit liver. The kinase catalyzed the incorporation of phosphate into the 22-k light chains of hepatocyte myosin, resulting in a 7-fold activation of the Mg(2+)-ATPase activity by F-actin. The kinase did not show any glycogen synthase kinase activity which has previously been shown to phosphorylate isolated chicken gizzard myosin light chain. ML-7, an inhibitor specific for smooth muscle myosin light chain kinase, inhibited the liver kinase with a Ki value of 13.2 microM.
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PMID:Partial characterization of a rabbit liver Ca(2+)-calmodulin-dependent kinase with myosin light chain phosphorylating activity. 839 18

1. Using beta-escin and ionomycin-treated skinned smooth muscle strips of the rabbit mesenteric artery, the effects of calyculin A (CL-A, an inhibitor of type 1 and 2A phosphatases) on mechanical activities, phosphorylation of myosin light chain (MLC) and the relationship between the two were studied in Ca(2+)-free solution containing 4 mM EGTA and these effects were compared with those evoked by Ca2+. 2. The threshold concentration of Ca2+ required to increase either tension or MLC-phosphorylation was 0.1 microM and maximum effects were obtained at 10 microM. MLC was mainly monophosphorylated, rather than diphosphorylated, in the presence of Ca2+. ED50 value for Ca2+ was 0.54 microM for either tension or MLC-phosphorylation. The relationship between tension and MLC-phosphorylation is linear in the pCa range 7-5.5. 3. In Ca(2+)-free solution (containing either 20 mM EGTA or 4 mM EGTA with or without 4 mM BAPTA), 3 microM CL-A produced a contraction, the maximum amplitude of which was similar to that evoked by 10 microM Ca2+. CL-A (0.03-3 microM) concentration-dependently increased both tension and MLC-phosphorylation in Ca(2+)-free solution containing 4 mM EGTA. The threshold concentration of CL-A required for the increase in either tension or MLC-phosphorylation was 0.03 microM and maximum effects were obtained at 3 microM. In the presence of CL-A, MLC was not only monophosphorylated but also diphosphorylated. ED50 values for CL-A were 0.39 microM for tension, 0.44 microM for the monophosphorylated form of MLC and 0.54 microM for all phosphorylated (mono + di) forms. The relationship between tension and the monophosphorylated form of MLC was linear over the concentration range studied and was similar to that for Ca2+. 4. H-7 (3 microM, an inhibitor of protein kinase C) inhibited neither the tension nor phosphorylation of MLC induced by 10 microM Ca2+ or 3 microM CL-A. At a high concentration (30 microM), H-7 slightly inhibited both the tension and phosphorylation of MLC induced by either stimulant without a change in the tension-MLC-phosphorylation relationship. KN-62, an inhibitor of Ca(2+)-calmodulin-dependent protein kinase II, did not modify either the tension or the phosphorylation of MLC induced by 10 microM Ca2+ or 3 microM CL-A. CK-II, another inhibitor of Ca(2+)-calmodulin-dependent protein kinase II, did not inhibit the contraction induced by 3 microM CL-A. 5. SM-1 (0.03-0.3 mM) and ML-9 (0.1 and 0.3 mM), inhibitors of MLC-kinase, each lowered the resting level of MLC-phosphorylation in Ca2+-free solution and also inhibited both the tension and MLC-phosphorylation induced by 10 microM Ca2+ or 3 microM CL-A, in a concentration-dependent manner.Neither SM-1 nor ML-9 modified the relationship between tension and either monophosphorylated or all phosphorylated (mono + di) forms of MLC in the presence of Ca2+ or CL-A.6. In a solution containing MgITP (the substrate for myosin ATPase but not for MLC-kinase) with no MgATP, 10 microM Ca2+ failed to produce contraction. Under these conditions, the amplitude of the contraction induced by 3 microM CL-A was greatly diminished in comparison with that induced in the presence of MgATP.7. The present results suggest that in smooth muscle cells of the rabbit mesenteric artery, CL-A in Ca2+-free solution, produces a maximum contraction through an indirect activation of Ca2+-calmodulin independent(constitutively active) MLC-kinase via its inhibitory action on MLC-phosphatases. Based on this evidence, it is hypothesized that, in these cells, a constitutively active MLC-kinase may be present, though its action may be concealed by that of endogenous MLC-phosphatase.
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PMID:Effects of calyculin A on tension and myosin phosphorylation in skinned smooth muscle of the rabbit mesenteric artery. 839 95

An active ribosomal protein S6 kinase has been highly purified from the membranes of rabbit reticulocytes by chromatography of the Triton X-100 extract on DEAE-cellulose, SP-Sepharose Fast Flow, and by FPLC on Mono Q and Superose-12. The S6 kinase elutes around 40 000 daltons upon gel filtration on Superose-12 or Sephacryl S-200. It has a subunit molecular weight of 40-43 kDa as determined by protein kinase activity following denaturation/renaturation in SDS-polyacrylamide gels containing S6 peptide. It also phosphorylates translational initiation factors eIF-2 and eIF-4F, glycogen synthase, histone 1, histone 2B, myelin basic protein, but not prolactin, skeletal myosin light chain, histone 4, tubulin, and casein. Apparent Km values have been determined to be 15 microM for ATP, 1.2 microM for S6 and 10 microM for S6 peptide. Two-dimensional tryptic phosphopeptide mapping shows the same sites on S6 are phosphorylated as those identified previously with proteolytically activated multipotential S6 kinase from rabbit reticulocytes, previously denoted as protease activated kinase II. Examination of relative rates of phosphorylation and kinetic constants of synthetic peptides based on previously identified phosphorylation sites, indicates a minimum substrate recognition sequence to be arginine at the n - 3 position. Based on these characteristics, including molecular weight and an expanded substrate specificity, the membrane S6 kinase can be distinguished from the p90 (Type I) and p70 (Type II) S6 kinases, and from protein kinase C and the catalytic subunit of cAMP-dependent protein kinase.
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PMID:A membrane-bound protein kinase from rabbit reticulocytes is an active form of multipotential S6 kinase. 859 70

The characteristics of actively growing smooth muscle cells (a variant, SM-3) were compared with those of growth-arrested cells with regard to response of myosin light chain (MLC) phosphorylation. Augmented MLC phosphorylation, in particular diphosphorylation, was observed in actively growing cells when stimulated with 30 microM prostaglandin F2alpha (PGF2alpha). The maximum level of diphosphorylation in growing cells was significantly higher than that in growth-arrested cells. The MLC diphosphorylation was sensitive to protein kinase C down-regulation by phorbol dibutylate and pretreatment by the protein kinase inhibitors, staurosporine (30 nM) and isoquinoline sulphonamide HA1077 (20 microM). The actively growing cells contained larger amounts of protein kinase C than growth-arrested cells. The phosphorylation sites of mono- and diphospho-MLC were determined to be MLC kinase-dependent sites (Thr18, Ser19). The PGF2alpha concentration/response curves of MLC diphosphorylation were shifted to the left and upwards in the presence of the protein phosphatase inhibitor calyculin A. These results suggest that PGF2alpha stimulation of actively growing SM-3 cells augments MLC kinase-dependent MLC diphosphorylation. Protein kinase C is involved indirectly in this reaction, possibly through MLC phosphatase-sensitive regulatory mechanisms.
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PMID:Myosin light chain diphosphorylation is enhanced by growth promotion of cultured smooth muscle cells. 866 62

This study sought to identify specific enzyme(s) involved in the biochemical cascade of inhibition of renin secretion through Ca(2+)-calmodulin mediation with the use of inhibitors of protein kinase and phosphatases. Inhibition of renin secretion mediated by Ca(2+)-calmodulin was induced by incubating rat renal cortical slices in K(+)-rich depolarizing medium, producing > 50% inhibition. This inhibition was completely blocked by the calmodulin antagonist calmidazolium. The inhibitor of protein kinase with broad specificity, K-252a, blocked the inhibition of renin secretion. Neither KN-62, a specific inhibitor of Ca(2+)-calmodulin-dependent protein kinase II (CaMK II), nor specific inhibitors of protein phosphatase 2B (PP2B), cyclosporin A and FK-506, blocked the inhibition. On the other hand, all four known inhibitors specific for myosin light chain kinase (MLCK), with different chemical structures and mechanisms of inhibition (ML-9, ML-7, KT-5926 and wortmannin), almost completely protected renin secretion against the inhibition by Ca2+. In particular, ML-9 reversively protected > 77% secretion against the inhibition both in K(+)-rich medium alone and in combination with the calcium ionophore A-23187 in a concentration-dependent manner. Together, these findings from our present study provide the first evidence, albeit indirect in nature, for the possibility that activation of Ca(2+)-calmodulin-dependent MLCK at the downstream of Ca2+ influx into juxtaglomerular (JG) cells leads to phosphorylation of 20-kDa regulatory myosin light chain (MLC20). Through interaction with actin, the phosphorylated MLC20 may play an important role in the inhibitory stimulus-secretion coupling of renin.
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PMID:Inhibition of renin secretion by Ca2+ through activation of myosin light chain kinase. 876 52

In smooth muscle and specific nonmuscle cells the phosphorylation of the regulatory myosin light chains by myosin light chain kinase (MLCK) is an obligatory step in actin-induced activation of myosin ATPase and subsequent contractile events. We have previously demonstrated that CaM phosphorylated by casein kinase II fails to activate bovine platelet MLCK (Sacks et al. (1992) Biochem. J. 283, 21-24). While myosin light chains are perceived as the only known substrate for MLCK phosphorylation activity, we now show that MLCK phosphorylates CaM. This phosphorylation of CaM is dependent upon the presence of basic peptides such as poly-L-arginine (optimal basic peptide/CaM ratio = 0.08) and is stimulated by saturating [Ca2+] (K0.5 = 16 microM). CaM phosphorylation was inhibited by KT5926, a specific MLCK inhibitor, with a dose-dependency identical to that for inhibition of myosin light chain phosphorylation. Native and MLCK-phosphorylated CaM were indistinguishable in activating MLCK to phosphorylate myosin light chains. Interestingly, MLCK in which the CaM-binding site has been removed is able to phosphorylate CaM in a Ca(2+)-independent manner, suggesting that two CaM molecules bind to intact MLCK simultaneously, one on the inhibitory (pseudosubstrate) domain and one at the catalytic site. CaM phosphorylation by MLCK occurred exclusively on Thr 29 (90%) and Thr 26 (10%) in the first Ca(2+)-binding pocket. In summary, CaM phosphorylation by MLCK differs from CaM phosphorylation catalyzed by other kinases (i.e., the insulin receptor or casein kinase II) in both basic peptide and Ca2+ requirements as well as in the sites of phosphorylation. Further investigations of this model may provide insight into the mechanisms of MLCK activation and substrate recognition.
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PMID:Phosphorylation of calmodulin in the first calcium-binding pocket by myosin light chain kinase. 880 14


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