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)

Angiotensin II, catecholamines, and vasopressin are thought to stimulate hepatic glycogenolysis and gluconeogenesis via a cyclic AMP-independent mechanism that requires calcium ion. The present study explores the possibility that angiotensin II and vasopressin control the activity of regulatory enzymes in carbohydrate metabolism through Ca2+-dependent changes in their state of phosphorylation. Intact hepatocytes labeled with [32P]PO43- were stimulated with angiotensin II, glucagon, or vasopressin and 30 to 33 phosphorylated proteins resolved from the cytoplasmic fraction of the cell by electrophoresis in sodium dodecyl sulfate polyacrylamide slab gels. Treatment of the cells with angiotensin II or vasopressin increased the phosphorylation of 10 to 12 of these cytosolic proteins without causing measurable changes in cyclic AMP-dependent protein kinase activity. Glucagon stimulated the phosphorylation of the same set of 11 to 12 proteins through a marked increase in cyclic AMP-dependent protein kinase activity. The molecular weights of three of the protein bands whose phosphorylation was increased by these hormones correspond to the subunit molecular weights of phosphorylase (Mr = 93,000), glycogen synthase (Mr = 85,000), and pyruvate kinase (Mr = 61,000). Two of these phosphoprotein bands were positively identified as phosphorylase and pyruvate kinase by affinity chromatography and immunoprecipitation, respectively. Incubation of hepatocytes in a Ca2+-free medium completely abolished the effects of angiotensin II and vasopressin on protein phosphorylation but did not alter those of glucagon. Treatment of hepatocytes with angiotensin II, glucagon, or vasopressin stimulated phosphorylase activity by 250 to 260%, inhibited glycogen synthase activity by 50%, and inhibited pyruvate kinase activity by 30 to 35% (peptides) to 70% (glucagon). The effects of angiotensin II and vasopressin on the activity of all three enzymes were completely abolished if the cells were incubated in a Ca2+-free medium while those of glucagon were not altered. The results imply that angiotensin II, catecholamines, and vasopressin control hepatic carbohydrate metabolism through a Ca2+-requiring, cyclic AMP-independent pathway that leads to the phosphorylation of important regulatory enzymes.
...
PMID:The role of calcium ion as a mediator of the effects of angiotensin II, catecholamines, and vasopressin on the phosphorylation and activity of enzymes in isolated hepatocytes. 22 57

beta-Adrenergic stimulation induces serotonin N-acetyltransferase (SNAT) activity in the rat pineal gland. The magnitude and some of the characteristics of this response vary as a function of the gland's previous exposure to stimulation. A period of stimulation results in a subsensitive response to subsequent stimulation. A period without stimulation provides a supersensitive response to subsequent stimulation. Investigations concerned with the mechanisms regulating the rat pineal's sensitivity to beta-adrenergic stimulation are described. These have focused on the regulation of cyclic AMP metabolism. Several of the components involved in the induction of SNAT activity appear to participate in the regulation of sensitivity. These include the beta-adrenergic binding sites, the catecholamine-sensitive adenylate cyclase, the cyclic nucleotide phosphodiesterase, and the cyclic AMP-dependent protein kinase. Thus, the rat pineal's sensitivity to beta-adrenergic stimulation appears to be regulated at multiple sites. Other investigations have focused on the regulation of pineal cyclic GMP metabolism. Unlike cyclic AMP, the stimulation of cyclic GMP synthesis requires the presence of intact nerve endings and of extracellular calcium. Some of the characteristics of pineal cyclic GMP regulation are described.
...
PMID:Sensitivity and cyclic nucleotides in the rat pineal gland. 22 42

A new multifunctional protein kinase, which normally exists as an inactive form in the soluble fraction in mammalian tissues, attaches to membranes to exhibit full enzymatic activity. A low concentration of Ca2+ is absolutely necessary for this activation. This process is reversible. cAMP shows no effect. The active factors in membranes are phosphatidylinositol, phosphatidylserine, phosphatidic acid, diphosphatidylglycerol, and phosphatidylethanolamine in that order. Phosphatidylcholine and sphingomyelin are far less effective. Cytoplasmic as well as other membrane fractions from various tissues are active in supporting the enzymatic activity. A possible role of this Ca2+ and phospholipid-activated protein kinase system in transmembrane control is proposed.
...
PMID:A role of membranes in the activation of a new multifunctional protein kinase system. 22 10

Cyclic AMP-dependent protein kinase has been well established to be composed of catalytic and regulatory subunits, and cyclic AMP acts to dissociate these subunits to exhibit full enzymatic activity. In contrast, cyclic GMP-dependent protein kinase does not possess such a subunit structure and is activated by cyclic GMP simply in an allosteric manner. In addition to cyclic AMP-dependent and cyclic GMP-dependent protein kinases, another species of multifunctional protein kinase has been found in many mammalian tissues. This protein kinase is entirely independent of cyclic nucleotides and activated by lower concentrations of Ca2+ in the presence of a membrane-associated factor. This factor has been identified as phospholipids; in fact, phosphatidylinositol and phosphatidylserine are active in this role, whereas lecithin and sphingomyelin are unable to activate the enzyme. Thus, the three species of protein kinases mentioned above are activated in different manners. Nevertheless, these enzymes show very similar substrate specificities and phosphorylate the same specific seryl residues of histone fractions. In addition, all enzymes have abilities to activate and inactivate muscle phosphorylase kinase and glycogen synthetase, respectively, although the relative rates of reactions towards various substrates are markedly different. The Ca2+-dependent protein kinase seems to be associated with membranous components, whereas cyclic GMP-dependent protein kinase appears to be related to certain subcellular organella such as nucleus. Suggestive evidence is available implying that the cyclic AMP-, cyclic GMP- and Ca2+-activated three sets of protein kinase systems may play each specific physiological roles presumably owing to their own subcellular compartments.
...
PMID:Regulatory and functional compartment of three multifunctional protein kinase systems. 22 57

Ca2+-dependent phosphorylation of the myosin light chains in bovine aortic native actomyosin is markedly depressed in the presence of cyclic AMP and its dependent protein kinase. This inhibition occurs with either cardiac, skeletal, or aortic protein kinase plus cyclic AMP, while little or no inhibition occurs with either cyclic AMP or protein kinase alone. The extent of inhibition is related to the concentration of protein kinase and approaches a maximum of approximately 50%. Concomitant with the inhibition of myosin light chain phosphorylation is (a) an increased phosphorylation of a 100,000-dalton moiety which possibly corresponds to the myosin light chain kinase present in the native actomyosin preparation and (b) a decrease in the actomyosin Mg2+-ATPase activity. These findings suggest that modulation of actin-myosin interactions by the cAMP system directly at the level of the contractile proteins may represent a mechanism by which beta adrenergic relaxation occurs in mammalian vascular smooth muscle.
...
PMID:Adenosine 3':5'-monophosphate-mediated inhibition of myosin light chain phosphorylation in bovine aortic actomyosin. 22 48

Histone kinase activity was purified from human polymorphonuclear leukocytes by ammonium sulphate precipitation of a 180 000 x g supernatant, followed by DEAE-cellulose chromatography and gelfiltration. On DEAE-cellulose cAMP dependent kinase activity eluted in two peaks, I and III, at 1.2 mmho and 6.5 mmho, respectively. Catalytic subunit (C) from both peaks had Mr 33 000, 3.0S. Regulatory subunit (R) from peak I and III both had Mr 33 000 upon gelfiltration, but sedimented at 2.8--3.0S and 3.0--3.2S, respectively. R2 and R4 subunits were identified. The R-C dimer from peak I and III sedimented at 4.8S and (4.8)--5.1S, respectively. The holoenzyme from peak I had Mr 165 000, 6.7S, which suggest a R2C2 structure, while that of peak III sedimented at 6.7S, but eluted at Mr 330 000 (2R2C2) by gelfiltration. The Kmapp for peak I and III enzymes were, respectively: histone IIA 0.5 mg/ml (both forms), ATP 18 microM and 23 microM, and cAMP 5 X 10(-8) M and 6.3 x 10(-8) M. Both enzymes had pH optimum 6.7--6.9 and were equally sensitive to Ca2+, temperature and protein kinase inhibitor. The substrate specificity was histone VS greater than histone IIA = histone VIS greater than casein greater than phosvitin. Peak I enzyme, but not peak III enzyme, was dissociated by histone and high ionic strength and reassociation of R and C subunits were facilitated by ATP-Mg. It is concluded that peak I and III enzymes represent type I and II cAMP dependent protein kinases, respectively. Type I comprises 20--30% of cAMP dependent protein kinase activity and is absent from the 180 000 x g supernatant of gently disrupted cells. Purified catalytic subunit had Kmapp (ATP) 20 microM with rabbit muscle glycogen synthease I as substrates. Synthase I from rabbit muscle and human leukocytes were phosphorylated by catalytic subunit to synthase D (ratio of independence less than 0.07). cAMP independent histone kinase activity eluted in one peak (Peak II) at3 mmho. The enzymatic activity sedimented at 3.4S and eluted from gelfiltration with Mr 78 000. Kmapp for ATP was 78 microM and for histone IIA 0.5 mg/ml. The enzyme was sensitive to temperature, but less sensitive than cAMP dependent protein kinase to Ca2+, and insensitive to protein kinase inhibitor. The substrate specificity was histone IIA greater than histone VS = histone VIS, while casein and phosvitin were poor substrates. Glycogen synthase I was not phosphorylated. The cAMP independent histone kinase activity comprised 15% of the total histone kinase activity in a crude homogenate of leukocytes. Its physiological substrate is unknown.
...
PMID:Purification and properies of cAMP dependent and independent histone kinases from human leukocytes. 22 66

Caclium initiates smooth muscle contraction by activating an enzyme, myosin light chain kinase. This enzyme catalyzes the transfer of phosphate from adenosine triphosphate to the 20,000 dalton light chain of myosin. In its phosphorylated form myosin interacts with actin to produce muscle contraction. The mechanism by which calcium activates myosin kinase requires (1) the binding of calcium to a 16,500 dalton calcium-binding protein (calmodulin), and (2) the binding of calmodulin-calcium to a 125,000 dalton catalytic subunit. This two protein complex is the active form of myosin light chain kinase. Smooth muscle relaxation is mediated by cyclic adenosine 3':5' monophosphate (cyclic AMP). One nechanism by which the latter may exert a direct effect on actin-myosin interaction is through the activation of a cyclic AMP-dependent protein kinase that can phosphorylate the 125,000 dalton component of myosin light chain kinase. Phosphorylation of myosin light chain kinase decreases the activity of the enzyme, thus favoring the unphosphorylated form of myosin, which cannot interact with actin to produce smooth muscle contraction.
...
PMID:Role of calcium and cyclic adenosine 3':5' monophosphate in regulating smooth muscle contraction. Mechanisms of excitation-contraction coupling in smooth muscle. 22 62

Recent results have indicated that alpha-adrenergic receptors are the major mediators of catecholamine actions on liver metabolism in several species. It is well-established that cAMP and cAMP-dependent protein kinase are not involved in hepatic alpha-adrenergic effects. This review presents evidence that alpha-adrenergic stimulation of glycogenolysis in rat liver involves the mobilization of Ca2+ ions from mitochondria and stimulation of phosphorylase kinase by the resulting increase in cytosolic Ca2+ concentration. Possible mechanisms by which activation of alpha-adrenergic receptors causes release of mitochondrial Ca2+ and affects other cell processes are discussed.
...
PMID:Mechanisms involved in alpha-adrenergic effects of catecholamines on liver metabolism. 22 45

The present study reports the effects of the lipophylic ionophore X537A on lipolysis and accumulation of cAMP in isolated hamster epidiymal adipocytes. X537A inhibited lipolysis activated with norepinephrine, isoproterenol, dibutyryl cAMP or theophylline but failed to influence basal lipolysis. The minimum effective concentration of X537A required to inhibit lipolysis was between 1 and 3 micrograms/ml; at a concentration of 10 micrograms/ml, X537A inhibited lipolysis by approximately 50%. The antilipolytic effect of X537A does not result from decreased formation of cAMP because the accumulation of cAMP in response to isoproterenol or theophylline was significantly potentiated in the presence of the ionophore. Most of the additional cAMP that accumulated in the presence of X537A was found to be intracellelular, the distribution of cAMP between cells and incubation medium not being influenced by X537A. Neither the basal activity of cAMP dependent protein kinase nor the activity in the presence of isoproterenol or theophylline was influenced by X537A. The effects of X537A on lipolysis and on accumulation of cAMP were found to persist in the absence of extracellular calcium, but adipocytes that were preincubated in a calcium free media containing 4.0 mM EGTA failed to respond to X537A with an increase in cAMP levels. It is concluded that X537A inhibits lipolysis by uncoupling cAMP accumulation from activation of triglyceride lipase by a mechanism unrelated to activation of protein kinase.
...
PMID:Inhibition of lipolysis in hamster adipocytes by the cation ionophor X537A. 22 46

In 32P incorporation experiments with intact adrenocortical cells, adrenocorticotropin (ACTH) or adenosine 3',5'-cyclic monophosphate (cAMP) induced a rapid and transient increase of approximately 300-500% in the phosphorylation of a 32P-containing cytoplasmic protein of about 150,000 daltons (APS150). Half-maximal stimulation of APS150 phosphorylation was observed with about 3 pM ACTH. Receptor-bound cAMP, corticosterone production, and the appearance of phosphorylated APS150 increased in parallel with respect to both time and ACTH concentration. All three responses were dependent on extracellular calcium. Inhibition of protein synthesis with cycloheximide suggested a half-life of APS150 of about 10 min. The time course of 32P incorporation into ACTH-induced APS150 in the absence and presence of nonradioactive phosphate shows that the phosphorylation of APS150 is under simultaneous control of cAMP-dependent protein kinase and of phosphoatase activity. Thus a rapid ACTH-dependent and cAMP-dependent protein phosphorylation in intact adrenocortical cells within steroidogenic ACTH concentrations has now been demonstrated.
...
PMID:Adrenocorticotropin (ACTH) induces phosphorylation of a cytoplasmic protein in intact isolated adrenocortical cells. 22 81


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

---