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)

A protein kinase, which was produced from its proenzyme occurring in rat brain upon limited proteolysis by a Ca2+-dependent protease from the same tissue (Inoue, M., Kishimoto, A., Takai, Y., and Nishizlka, Y. (1977) J. Biol. Chem. 252, 7610-7616, was capable of phosphorylating alpha and beta subunits of rabbit skeletal muscle glycogen phosphorylase kinase, resulting in a marked enhancement of the enzymatic activity. This protein kinase was entirely independent of cyclic nucleotides and differed from the catalytic subunit of cyclic AMP-dependent protein kinase. The activation of phosphorylase kinase by this active protein kinase was not inhibited by a protein inhibitor of cyclic AMP-dependent protein kinase, nor by ethylene glycol bis(beta-aminoethyl ether)N',N'-tetraacetic acid, which prevented autophosphorylation of phosphorylase kinase. The proenzyme was distinguishable from cyclic nucleotide-dependent protein kinases, since it did not bind cyclic AMP and cyclic GMP, and was inactive in the phosphorylation and activation of phosphorylase kinase both in the presence and absence of these cyclic nucleotides. Neither the protein kinase nor its proenzyme showed phosphorylase kinase activity. Available evidence indicates that the Ca2+-activated, cyclic nucleotide-independent protein kinase system as well as cyclic AMP-dependent protein kinase shows an ability to stimulate glycogen breakdown as far as tested in vitro.
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PMID:Activation of glycogen phosphorylase kinase by a calcium-activated, cyclic nucleotide-independent protein kinase system. 91 21

Under conditions favoring its autocatalytic reaction, phosphorylase kinase may be activated and phosphorylated in 2-(N-morpholino)ethanesulfonate (Mes) buffer to a much higher level than in beta-glycerophosphate buffer. The fact that the reaction is autocatalytic is supported by several observations: (a) the progress curve of the reaction exhibits a pronounced lag phase, (b) the reaction is strongly inhibited by ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetate, which inhibits phosphorylase kinase, (c) the pH profile of the reaction resembles that of the phosphorylase b to a reaction as catalyzed by nonactivated phosphorylase kinase, and (d) the reaction is not significantly affected by adenosine 3':5'-monophosphate (cAMP) nor by the heat-stable protein inhibitor of cAMP-dependent protein kinases. When fully autoactivated, phosphorylase kinase possesses an activity that is 100% higher than that of the protein kinase-activated form. The results suggest that autophosphorylation of phosphorylase kinase may be an important regulatory mechanism. The autocatalytic reaction involves phosphorylation of the two larger subunits of phosphorylase kinase, i.e. subunits A and B, with a combined total of 7 to 9 phosphates incorporated per mol of enzyme. Although the cAMP-dependent protein kinase also catalyzes the phosphorylation of subunits A and B, the two mechanisms of phosphorylation appear to involve different sites. Prior phosphorylation of phosphorylase kinase by the protein kinase has little effect on the level of autophosphorylation. Thus activation of phosphorylase kinase may be brought about by phosphorylation of the enzyme at different sites.
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PMID:A study on the autoactivation of rabbit muscle phosphorylase kinase. 94 93

Meiosis reinitiation has been triggered by injection of beef heart protein kinase or rabbit phosphorylase kinase into Xenopus laevis oocytes. Successful injections are followed by germinal vesicle breakdown, chromosome condensation, formation of a normal meiotic spindle, and appearance of an amplifiable maturation promoting factor. Meiosis reinitiation does not occur when the enzymes are introduced into the oocytes simultaneously with EGTA or after pretreatment with cycloheximide. Antipain, an antiprotease which abolishes the response of oocytes to progesterone, does not suppress the meiosis reinitiation induced by injection of protein kinase or phosphorylase kinase.
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PMID:Induction of meiosis by injection of heterologous protein kinase and phosphorylase kinase in Xenopus laevis oocytes. 96 20

The inhibition of phosphorylase kinase catalytic activity by 0.1 M neutral salts was predicted by the Hofmeister series of anions. The site of action of the salts was determined by the following evidence to be on the phosphorylase kinase molecule directly, rather than on its protein substrate. (1) Nonactivated kinase was more sensitive to salt inhibition than the activated form. (2) Ca2+ partially overcame the inhibition of nonactivated kinase. (3) Inhibition by Cl- occurred with either phosphorylase or a tetradecapeptide containing the convertible seryl residue as substrate. (4) Phosphorylation of nonactivated phosphorylase kinase by protein kinase was markedly inhibited by NaNO3, but this salt had little effect on the phosphorylation of histone by protein kinase. The influence of neutral salts on phosphorylase kinase activity was biphasic. Although activity was inhibited at low salt concentrations, it actually was stimulated as the salt concentration was increased. A similar biphasic response to various salt concentrations was observed in the velocities of autophosphorylation of phosphorylase kinase. The lag in the rate of product formation seen during the activity assay was less pronounced at inhibitory salt concentrations and was abolished at stimulatory salt concentrations. How the influence of salts relates to autophosphorylation and the lag is considered.
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PMID:Site of action and biphasic effect of neutral salts in the phosphorylase kinase reaction. 97 70

Autoactivation of phosphorylase kinase in the presence of substrates has been studied to determine the cause of the hysteresis, or lag, in the phosphorylase kinase reaction. Peptide analogs corresponding to the convertible serine region of phosphorylase have been used as low molecular weight alternative substrates. Autophosphorylation of the kinase molecule was measured under conditions that favored autoactivation. Phosphorylase b and a tetradecapeptide, which was found to be a good model of phosphorylase, stimulated autoactivation by 86- and 37-fold, respectively. The tetradecapeptide also stimulated autophosphorylation of subunits A and B of the kinase molecule. This increased autophosphorylation coincided with an increased ability to convert phosphorylase. This finding supports the hypothesis that autophosphorylation is responsible for the lag in the phosphorylase kinase reaction. No evidence was obtained to suggest that the lag could be due to dissociation of the kinase. The stoichiometry of phosphate incorporation into phosphorylase kinase subunits by autophosphorylation was much greater than that reported to occur by protein kinase phosphorylation. Multiple phosphorylation sites in subunit A accounted for most of the phosphate incorporation during autophosphorylation. Saturating levels of hexa- and octapeptide analogs also caused stimulation of autophosphorylation. Possible mechanisms and experimental implications of substrate-stimulated autophosphorylation are discussed. Consideration also is given to the possible role of effectors in autophosphorylation in vivo.
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PMID:Stimulation of phosphorylase kinase autophosphorylation by peptide analogs of phosphorylase. 100 97

Distinct isoenzyme patterns of the glycogenolytic enzymes exist in different fibre types. Fast twitch glycolytic and slow twitch oxidative fibres differ in the proportion of the two isoenzymes of cyclic AMP dependent protein kinase and in the type of phosphorylase kinase that is present. Slow twitch oxidative fibres and cardiac fibres resemble one another in these two respects, but differ in that the type I phosphorylase of cardiac muscle is absent in slow twitch oxidative fibres. In all examples, the functional differences between the isoenzymes seem to be related to the regulatory rather than the catalytic behavior of the molecules. In the case of cyclic AMP dependent protein kinase and phosphorylase kinase, it is a regulatory subunit that appears to be affected [16,23], while in the case of phosphorylase, the type I isoenzyme is known to have a five to eight-fold Ka for the allosteric activator 5' AMP [6]. However, the precise physiological significance of these differences remains to be elucidated.
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PMID:Distribution of isoenzymes of the glycogenolytic cascade in different types of muscle fibre. 106 84

Phosphorylase kinase was activated 5--10-fold in vivo by an intravenous injection of adrenalin. Sodium fluoride an inhibitor of phosphorylase kinase phosphatase, was required to prevent the reversal of this process; the activated and non-activated forms of the enzyme were indistinguishable by dodecylsulphate gel electrophoresis. This suggested that the activation had resulted from a phosphorylation of the enzyme, and that it was not a consequence of the well known activation by proteolytic cleavage that can be demonstrated in vitro. Phosphorylase kinase activated in vivo was purified and digested with trypsin, and the two tryptic peptides which contain the serine residues which are phosphorylated in vitro by the action of cyclic-AMP (adenosine 3':5'-monophosphate) dependent protein kinase, were isolated. It was found that the same nine-amino-acid segment of the beta chain and the same seven-amino-acid segment of the alpha chain had become phosphorylated in vivo in response to adrenalin, as were phosphorylated in vitro. The degree of phosphorylation of each of the two sites was at least 50%. The data provide direct proof that the activation of phosphorylase kinase which occurs in vivo in response to adrenalin results from a phosphorylation of the enzyme. They also indicate that the novel form of regulation associated with the phosphorylation of the alpha subunit, the stimulation of protein dephosphorylation by "second site phosphorylation", can now be regarded as a new form of enzyme control mechanism which operates in vivo. The regulation of phosphorylase kinase activity was studied in the protein - glycogen complex from skeletal muscle. The enzyme could be rapidly converted to a phosphorylated form in a cyclic-AMP-stimulated reaction upon addition of magnesium ions and ATP, but the conversion of phosphorylase b to phosphorylase a in the complex still showed an absolute requirement for calcium ions. The implications of these findings and major problems in the hormonal control of skeletal muscle glycogenolysis which are not yet resolved, are discussed.
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PMID:The hormonal control of activity of skeletal muscle phosphorylase kinase. Phosphorylation of the enzyme at two sites in vivo in response to adrenalin. 112 18

In contrast to the mammalian enzyme, PFK from the nematode Ascaris suum is activated following phosphorylation (Daum et al. (1986) Biochem. Biophys. Res. Commun. 139, 215-221) catalyzed by a cAMP-dependent protein kinase (Thalhofer et al. (1988) J. Biol. Chem. 263, 952-957). In the present report, we describe the characterization of the major PFK dephosphorylating phosphatases from Ascaris muscle. Two of these phosphatases exhibit apparent M(r) values of 174,000 and 126,000, respectively, and are dissociated to active 33 kDa proteins by ethanol precipitation. Denaturing electrophoresis of each of the enzyme preparations showed two bands of M(r) 33,000 and 63,000. The enzymes are classified as type 2A phosphatases according to their inhibition by subnanomolar concentrations of okadaic acid, the lack of inhibition by heat-stable phosphatase inhibitors 1 and 2, and their preference for the alpha- rather than for the beta-subunit of phosphorylase kinase. Like other type 2A phosphatases, they exhibit broad substrate specificities, are activated by divalent cations and polycations, and inhibited by fluoride, inorganic phosphate and adenine nucleotides. In addition, we have found that PFK is also dephosphorylated by an unusual protein phosphatase. This exhibits kinetic properties similar to type 2A protein phosphatases, but has a distinctly lower sensitivity towards inhibition by okadaic acid (IC50 approx. 20 nM). Partial purification of the enzyme provided evidence that it is composed of a 30 kDa catalytic subunit and probably two other subunits (molecular masses 66 and 72 kDa). The dephosphorylation of PFK by protein phosphatases is strongly inhibited by heparin. This effect, however, is substrate-specific and does not occur with Ascaris phosphorylase a.
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PMID:Characterization of the major phosphofructokinase-dephosphorylating protein phosphatases from Ascaris suum muscle. 132 72

Messenger RNA encoding a protein kinase closely related to the catalytic subunit of skeletal muscle phosphorylase kinase has previously been isolated from a human HeLa cell cDNA library, and cross-species Northern hybridization analysis has shown that the rat homolog of this transcript is abundant in the adult testis (Hanks, S.K. (1989) Mol. Endocrinol. 3, 110-116). We now propose that the protein encoded by this transcript be designated as "PhK-gamma T." In this article, the primary structure of the rat homolog of PhK-gamma T is described, as deduced from nucleotide sequences of cDNA and genomic clones. RNase protection analysis reveals that PhK-gamma T transcripts are actually present in a wide variety of adult rat tissues, but at levels 20-100-fold less than what is observed in the testis. In the testis, transcription of the PhK-gamma T gene is initiated at multiple sites as shown by RNase protection and primer extension. Enzymatic activity of PhK-gamma T was demonstrated using renatured bacterially expressed protein. In the presence of Ca2+/calmodulin, PhK-gamma T is able to efficiently phosphorylate glycogen phosphorylase and convert it from an inactive to an active form. We conclude that PhK-gamma T represents a true isoform of phosphorylase kinase catalytic subunit.
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PMID:Molecular cloning and enzymatic analysis of the rat homolog of "PhK-gamma T," an isoform of phosphorylase kinase catalytic subunit. 137 Apr 75

1. Guinea-pig liver contained more phosphorylase in the active (phosphorylated) form and less synthase in the active (dephosphorylated) form when compared with rat liver. 2. Activities of cyclic AMP-dependent protein kinase and Ca(2+)-dependent phosphorylase kinase were the same in rat and guinea-pig livers. 3. Activities of phosphorylase phosphatase and synthase phosphatase in the extract and glycogen plus microsomal fraction of guinea-pig liver were significantly lower than those of rat liver. 4. The existence of inhibitor-1 in the liver of guinea-pig can maintain a lower activity of type-1 protein phosphatase, especially when inhibitor-1 is phosphorylated by cyclic AMP-dependent protein kinase.
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PMID:Comparative characterization of liver glycogen metabolism in rat and guinea-pig. 145 30


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