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)

The level of phosphorylation of myosin regulatory light chain in BALB/c 3T3 and certain other cultured substrate-attached fibroblasts has been shown to be altered by several agents which influence cell shape, attachment and/or surface receptors. This was investigated by metabolic labelling with [32P]orthophosphate, followed by exposure of the cells to the chosen conditions, rapid freezing to 'fix' phosphorylation levels, extraction and concentration in the presence of kinase and phosphatase inhibitors, and final analysis by two-dimensional gel electrophoresis. Gel patterns were interpreted by comparison with immunoprecipitates with antiserum to mouse nonmuscle myosin. Treatment of cells either with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or dibutyryl-cAMP suppressed light chain phosphorylation as predicted from the control mechanisms proposed previously from in vitro studies for Ca++ calmodulin and cAMP-dependent protein kinase respectively. Other effects were less easily explained: in BALB/c 3T3 cells, contrasting with previously reported behaviour of CHO cells, the cAMP-induced decline was small and transitory; and in at least one cell line (16C) the EGTA-induced decline was preceded by a strong pulse of enhanced phosphorylation. A striking and unexpected result was that azide, almost certainly acting on mitochondrial function, caused myosin light chain phosphorylation to be maintained over a long period even in the presence of EGTA which would otherwise bring about an immediate drop. The cleavage (by trypsin) or binding (by con A) of surface receptors was also shown to trigger the biochemical modulation of cellular myosin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myosin light chain phosphorylation in fibroblast shape change, detachment and patching. 379 39

One of the two regulatory light chains, RLC-a, of scallop smooth muscle myosin was fully phosphorylated by myosin light chain kinase of chicken gizzard muscle. The residue phosphorylated was Ser. It may be the Ser at number 11 from the N-terminal. The sequence of 9 residues around the Ser-11, QRATSNVFA, is identical with that around the phosphorylatable Ser of LC20 of chicken gizzard myosin. RLC-a was also phosphorylated slowly by cAMP-dependent protein kinase. The phosphorylation of RLC-a may be involved in the regulatory system for the catch contraction of scallop muscle.
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PMID:Phosphorylation of regulatory light chain a (RLC-a) in smooth muscle myosin of scallop, Patinopecten yessoensis. 384 Aug 2

In the present study, human islets were isolated by collagenase digestion from the pancreases of three kidney donors. Maintainance of the islets in tissue culture enabled insulin release, glucose oxidation and Ca2+ -calmodulin-dependent protein phosphorylation to be determined using the same islets. Increasing glucose over a range 0-20 mmol/l resulted in a sigmoidal stimulation of insulin release (28.8 +/- 5.2 to 118.4 +/- 25.8 microU . islet-1 . h-1, n = 10; threshold less than 4 mmol/l). There was a marked correlation between the insulin secretory response of the islets to glucose and their rate of glucose oxidation (5.9 +/- 0.3 at glucose 2 mmol/l up to 25.8 +/- 1.8 pmol . islet-1 . h-1 at 20 mmol/l, r = 0.98). N-acetylglucosamine (20 mmol/l) failed to elicit a secretory response from the islets. Stimulation of insulin secretion by glucose was dependent upon the presence of extracellular Ca2+. Extracts of the islets contained a Ca2+ -calmodulin-dependent protein kinase which phosphorylated a 48-kdalton endogenous polypeptide. Myosin light-chain kinase activity was demonstrated in the presence of exogenous myosin light chains. This report demonstrates for the first time the sigmoidal nature of glucose-stimulated insulin release from isolated human islets, and its correlation with enhanced glucose oxidation. Furthermore, this is the first report of the presence of Ca2+ -dependent protein kinases in human islets.
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PMID:Properties of isolated human islets of Langerhans: insulin secretion, glucose oxidation and protein phosphorylation. 388 20

In previous studies, we described a soluble Ca2+/calmodulin-dependent protein kinase which is the major Ca2+/calmodulin-dependent microtubule-associated protein 2 (MAP-2) kinase in rat brain [Schulman, H. (1984) J. Cell Biol. 99, 11-19; Kuret, J. A., & Schulman, H. (1984) Biochemistry 23, 5495-5504]. We now demonstrate that this protein kinase has broad substrate specificity. Consistent with a multifunctional role in cellular physiology, we show that in vitro the enzyme can phosphorylate numerous substrates of both neuronal and nonneuronal origin including vimentin, ribosomal protein S6, synapsin I, glycogen synthase, and myosin light chains. We have used MAP-2 to purify the enzyme from rat lung and show that the brain and lung kinases have nearly indistinguishable physical and biochemical properties. A Ca2+/calmodulin-dependent protein kinase was also detected in rat heart, rat spleen, and in the ring ganglia of the marine mollusk Aplysia californica. Partially purified MAP-2 kinase from each of these three sources displayed endogenous phosphorylation of a 54 000-dalton protein. Phosphopeptide analysis reveals a striking homology between this phosphoprotein and the 53 000-dalton autophosphorylated subunit of the major rat brain Ca2+/calmodulin-dependent protein kinase. The enzymes phosphorylated MAP-2, synapsin I, and vimentin at peptides that are identical with those phosphorylated by the rat brain kinase. This enzyme may be a multifunctional Ca2+/calmodulin-dependent protein kinase with a widespread distribution in nature which mediates some of the effects of Ca2+ on microtubules, intermediate filaments, and other cellular constituents in brain and other tissues.
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PMID:Ca2+/calmodulin-dependent microtubule-associated protein 2 kinase: broad substrate specificity and multifunctional potential in diverse tissues. 407 98

1. The low-molecular-weight components of myosin from rabbit skeletal muscle migrated as four bands on polyacrylamide-gel electrophoresis in 8m-urea but only as three in systems containing sodium dodecyl sulphate. The two bands of intermediate mobility in 8m-urea (Ml(2) and Ml(3)) had identical mobilities in sodium dodecyl sulphate. 2. The isolation of pure samples of all four low-molecular-weight components by DEAE-Sephadex chromatography is described. 3. The amino acid compositions of components Ml(2) and Ml(3) were identical. Further analyses showed the presence of 1 mol of phosphate/18500g of component Ml(2) and less than 10% of this amount in component Ml(3). Neither light component contained ribose. 4. Alkaline phosphatase from Escherichia coli converted component Ml(2) into Ml(3). Incubation with crude preparations of phosphorylase b kinase or protein kinase in the presence of ATP converted component Ml(3) into Ml(2). 5. Phosphorylation of component Ml(3) with the kinases isolated from skeletal muscle and [gamma-(32)P]ATP gave incorporation of (32)P only into component Ml(2) whether whole myosin or separated low-molecular-weight components were used. 6. High-voltage electrophoresis at pH6.5 and pH1.8 of a chymotryptic digest of (32)P-labelled component Ml(2) yielded one major radioactive peptide containing serine phosphate. 7. The amino acid sequence of this peptide was shown to be: Arg-Ala-Ala-Ala-Glu-Gly-Gly-(Ser,Ser(P))-Asn-Val-Phe. This sequence shows no obvious similarity to the site phosphorylated in the conversion of phosphorylase b into phosphorylase a by phosphorylase b kinase. 8. Evidence suggests that in vivo all the 18500-molecular-weight light chain is in the phosphorylated form. The extent of dephosphorylation that occurred during myosin extraction depended on the conditions employed.
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PMID:A phosphorylated light-chain component of myosin from skeletal muscle. 477 66

Modulation of the functional properties of the contractile proteins of mammalian heart muscle plays a significant role in the response of the heart to beta-adrenergic stimulation. The most well understood modification is a change in the concentration of calcium ions that is required to activate the contractile system. By means of a cAMP-sensitive phosphorylation of the inhibitory subunit of troponin (TNI), the threshold concentration for activation can be increased as much as 5-fold without changing the maximum calcium-activated force. The protein kinase involved in this regulation is located in the sarcolemma. Cholinergic stimulation causes a dephosphorylation of TNI by a cGMP-sensitive phosphatase. The concentration of calcium ions required to activate contraction also decreases as muscle length increases. This response of the contractile proteins does not involve phosphorylation of TNI. Regulation of the maximum calcium-activated force can take place by a cAMP-sensitive reaction involving a different protein kinase that is located inside the cell. This mechanism involves at least two sequential reactions, one a cAMP-controlled phosphorylation of a protein bound to an intracellular membrane to release an active factor, and the second, an interaction between the active factor and the contractile proteins to enhance the capacity for generating force in the presence of calcium. Phosphorylation of the light chain of myosin is produced by a calmodulin-regulated kinase. The light chain of myosin is partially phosphorylated in the intact heart, but beta-adrenergic stimulation of the heart does not increase the decrease of phosphorylation in parallel with the increase in contractility.
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PMID:Regulation of cardiac contractile proteins. Correlations between physiology and biochemistry. 609 39

In smooth muscle the Mr 20,000 light chain of myosin is phosphorylated by a calmodulin-dependent protein kinase. It consists of 2 subunits: calmodulin, an acidic protein of Mr 17,000 that binds 4 moles of Ca2+; and a larger protein of Mr circa 130,000. Activation of the kinase is dependent upon their association in the presence of Ca2+. Cyclic AMP-dependent protein kinase phosphorylation of the myosin light chain kinase occurs at 2 sites. It decreases the affinity of the kinase for calmodulin and a reduction in the rate of light chain phosphorylation occurs. The kinase has an overall asymmetric shape composed of a globular head and tail region for the skeletal muscle enzyme. Trypsin digestion of this kinase releases a fragment of Mr 36,000 from the globular region that contains the catalytic and calmodulin binding sites. Chymotrypsin digestion of the kinase from smooth muscle generates a fragment of Mr 80,000 that does not contain the calmodulin binding or cyclic AMP-dependent protein kinase phosphorylation sites. It is a Ca2+-independent form of the kinase that phosphorylates the light chain of myosin. These structural features indicate a regulatory role for the kinase in smooth muscle phosphorylation and contraction.
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PMID:Structure and function of a calmodulin-dependent smooth muscle myosin light chain kinase. 609 32

The 20,000-dalton light chain of myosin from chicken gizzard has been shown to be phosphorylated in a Ca2+ and calmodulin-independent manner by the activated form of a protease-activated kinase from rabbit reticulocytes. Protease-activated kinase I incorporates phosphate stoichiometrically into the phosphorylatable light chain (P-light chain) in isolated myosin light chains and in actomyosin. The same serine residue appears to be phosphorylated by the protease-activated kinase and the Ca2+-dependent myosin light chain kinase. This conclusion is based on results from two-dimensional peptide maps of chymotryptic and tryptic digests of the phosphorylated P-light chain and from phosphoamino acid analysis of acid hydrolysates. Phosphorylation of the P-light chain by the proteolytically activated protein kinase stimulates the actin-activated Mg-ATPase activity of myosin in the absence of Ca2+. The extent of stimulation of the ATPase activity is similar to that observed upon phosphorylation of actomyosin by the Ca2+-dependent myosin light chain kinase. A proteolytically activated protein kinase with chromatographic properties and substrate specificity similar to protease-activated kinase I from reticulocytes has also been identified in gizzard. Protease-activated kinase I has been shown to be distinct from the Ca2+-dependent myosin light chain kinase by the mode of activation and specificity with other substrates, including phosphorylation of a unique site on myosin P-light chain from skeletal muscle (Tuazon, P. T., Stull, J. T., and Traugh, J. A. (1982) Biochem. Biophys. Res. Commun. 108, 910-917).
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PMID:Activation of actin-activated ATPase in smooth muscle by phosphorylation of myosin light chain with protease-activated kinase I. 614 87

Myosin was isolated from extracts of a clonal cell line of pheochromocytoma (PC12) cells by ammonium sulfate fractionation and gel filtration. This myosin consisted of heavy chains and two light chains (20 and 17 kDa). The 20 kDa light chain could be phosphorylated by a protein kinase which was also present in the extracts and which eluted after myosin from the gel filtration column. Myosin phosphorylation was partly inhibited by EGTA and by the calmodulin-inhibiting drug trifluoperazine. The Mg2+-ATPase of phosphorylated myosin, but not of unphosphorylated myosin, was activated by skeletal muscle actin. Ca2+ did not affect the Mg2+-ATPase activity of either myosin preparation at low ionic strength. The phosphorylation of myosin may activate a contractile mechanism controlling the Ca2+-dependent secretion of norepinephrine from the cells.
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PMID:Myosin and myosin phosphorylation in pheochromocytoma (PC12) cells. 614 68

The aim of experiments described here was to test whether deactivation of cardiac myofibrils in acidic pH is associated with decreases in amounts of calcium bound to myofilament troponin. We determined the amounts of myofibrillar bound calcium attributable to troponin, from measurements of calcium binding to myofibrils and to myosin and from determination of the troponin C content of the myofibrillar preparations (0.40 nmol troponin C/mg protein). In measurements done at 2 mM free magnesium, 2 mM (magnesium-adenosine triphosphate, ionic strength 0.12, 22 degrees C, the pCa50 (-log of the half maximally activating molar free calcium) for myofibrillar magnesium-adenosine triphosphatase activity was 5.87 at pH 7.0, 5.49 at pH 6.5, and 5.04 at pH 6.2. This change in calcium sensitivity of myofibrillar magnesium-adenosine triphosphatase activity was present whether or not ethyleneglycol-bis(beta-aminoethyl ether)-N, N'-tetraacetic acid, was used to buffer the free calcium and whether or not myofibrillar troponin I had been phosphorylated by cyclic adenosine 3',5'-monophosphate-dependent protein kinase. However, the change in pCa50 of myofibrillar adenosine triphosphatase activity induced by acidic pH, was greater when free magnesium was reduced from 2.0 to 0.05 mM, and less when free magnesium was increased from 2.0 mM to 10 and 15 mM. The change in pCa50 with acidic pH was less if the ionic strength was reduced from 0.12 to 0.035 M. The magnesium-adenosine triphosphatase activity of troponin/tropomyosin-free myofibrils was independent of pCa and unaffected by a reduction of pH from 7.0 to 6.5. The affinity of myofibrillar troponin C for calcium decreased as pH was reduced from 7.0 to 6.5 and to 6.2 with and without ethyleneglycolbis(beta-aminoethyl ether)-N,N'-tetraacetic acid, and in a manner predicted from the effect of acidic pH on pCa50 for myofibrillar activation. Our results are consistent with the idea that at least part of the mechanism responsible for deactivation of the adenosine triphosphatase activity of cardiac myofilaments in acidic pH is a reduction in the affinity of myofibrillar troponin C for calcium.
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PMID:Inhibition of the activation and troponin calcium binding of dog cardiac myofibrils by acidic pH. 623 79


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