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)

cAMP-dependent protein kinase activity was present in a soluble TSH receptor fraction. The Km of this enzyme was 2.2 X 10(-6) M for casein substrate in the absence or presence of 10(-5) M cAMP. A [3H]cAMP-binding protein was also found in this fraction. The Ka for [3H]cAMP-binding was 0.11 X 10(6) M-1, with a total binding capacity of 3 nmol/mg protein. After fractionation using a continuous sucrose density gradient, one of the several [125I]iodobovine TSH-binding peaks corresponded to a [3H]cAMP-binding peak. After fractionation on a sucrose density gradient containing 0.4 M NaCl at pH 6.5, a major peak of protein kinase activity was shown. This protein kinase activity was stimulated by adding 10(-5) M cAMP. A peak of [3H]cAMP-binding activity corresponded to the same peak. Protein kinase activity in the receptor fraction was stimulated by adding 6 mg/ml bovine TSH. The soluble TSH receptor fraction also has an adenylate cyclase activity stimulated by TSH. These results suggest that some TSH receptors released from thyroid plasma membranes have associated adenylate cyclase activity and cAMP-dependent protein kinase activity. The receptor, cyclase, and kinase activities may exist in a functional primary receptor unit which is spontaneously released from plasma membranes.
...
PMID:Adenosine 3',5'-monophosphate-dependent protein kinase activity in soluble thyrotropin receptor complex. 22 Nov 90

LH-induced desensitization of the adenylyl cyclase system in a cell-free membrane preparation from preovulatory porcine follicles exhibits a critical dependence upon Mg and ATP (1). The membrane-rich preparation was found to contain endogenous cAMP-dependent and cAMP-independent protein kinases as well as phosphorprotein phosphatases. Endogenous phosphatase activity was enchanced by by Mn2+ and dithiothreitol. The addition of either Mn2+ or dithiothreitol to the porcine follicular membrane preparation incubated under desensitizing conditions promoted a specific concentration-dependent reversal of the LH-induced desensitization of the adenylyl cyclase system. The addition of exogenous phosphoprotein phosphatase, partially purified from procine follicular cytosol, also reversed LH-induced desensitization in a concentration-dependent manner. Boiling of the phophatase preparation prevented reversal of desensitization. The addition of either exogenous beef heart cAMP-dependent protein kinase or heat-stable protein kinase inhibitor did not modify LH-induced desensitization of the follicular adenylyl cyclase system. These results provide indirect evidence that while LH-induced desensitization is not mediated by a cAMP-dependent protein kinase, reversal of desensitization can be promoted by activation of endogenous phosphatase and the addition of a homologous phosphatase preparation.
...
PMID:Resensitization of the desensitized follicular adenylyl cyclase system to luteinizing hormone. 22 Nov 92

A heat-stable protein which inhibits cAMP dependent protein kinase was prepared from the bovine thyroid 100,000 X g supernatant. This protein inhibited the cAMP-dependent protein kinase both from bovine thyroid cytosol and bovine thyroid plasma membranes. The inhibitory effect was noncompetitive with histone as substrate of the cytosolic enzyme. The stimulatory modulator for cGMP-dependent protein kinase was separated from the 100,000 X g supernatant by Sephadex G-100 gel filtration. The stimulatory modulator had no stimulating effect on cAMP-dependent phosphorylation, and the inhibitory modulator of cAMP-dependent enzyme had no effect on cGMP-requiring phosphorylations. The inhibitory modulator may regulate cAMP-dependent protein kinase activity in cytosol and plasma membrane, and the stimulatory modulator for cGMP-dependent protein kinase may have a role in thyroid function independent of the cAMP-requiring system.
...
PMID:Cyclic nucleotide-dependent protein kinase modulators in thyroid tissue. 22 Dec

The sequences of two phosphopeptides isolated from the catalytic subunit of bovine cardiac muscle cAMP-dependent protein kinase (type II) and from two of its cyanogen bromide fragments, have been determined. One phosphorylation site is a threonyl residue located approximately 180 residues from the blocked NH2 terminus. Its sequence is: -Gly-Arg-Thr-Trp-Thr(P)-Leu-Cys- and includes one of the three sulfhydryl groups present in the molecule. The second phosphorylated site within the sequence: -Val-Ser(P)-Ile-Asn- is located towards the carboxyl end of the protein where the other 2 cysteinyl residues also reside. The finding that phosphorylation of the catalytic subunit occurs on two discrete sites rather than at random suggests that it might be of physiological importance, e.g. in the regulation of enzyme activity.
...
PMID:Sequence of two phosphorylated sites in the catalytic subunit of bovine cardiac muscle adenosine 3':5'-monophosphate-dependent protein kinase. 22 92

A series of 2'-O-acyl derivatives of 6-thioinosine cyclic 3',5'-phosphate (6-HS-cRMP) were prepared and examined for their cytotoxic effects on S49 mouse lymphoma cells which were deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). Cytotoxicity increased with the lipophilicity of the acyl group to a lowest EC50 of 65 micrometer for the 2'-O-palmityl derivative. Addition of a mutation in the gene for cAMP-dependent protein kinase to the HGPRTase-deficient cell line confers resistance to 2'-O-butyryl-cAMP but not to 2'-O-butyryl-6-HS-cRMP, indicating that the latter does not exert its toxic effect via activation of protein kinase. The time course of cell kill by 2'-O-palmityl-6-HS-cRMP resembled that of 6-mercaptopurine and not that of cyclic AMP in these cells. The data suggest that the intact cyclic nucleotides are penetrating the cells and being converted, by phosphodiesterase action and deacylation, to the first toxic metabolite of 6-mercaptopurine, thioinosinic acid.
...
PMID:2'-O-Acyl-6-thioinosine cyclic 3',5'-phosphates as prodrugs of thioinosinic acid. 22 58

The effect of catecholamines on membrane-associated protein kinase in the mature human erythrocyte was investigated. Protein kinase activity was assayed after isolation of membranes from intact erythrocytes incubated with and without catecholamines. Activation of the enzyme is expressed as the ratio of the extent of phosphorylation of exogenous protein substrate in the absence to that in the presence of 2.5 microM cyclic AMP (cAMP). The potent beta-adrenergic agonist, (-)isoproterenol (2 microM), (-)epinephrine (10 microM) and (-)norepinephrine (10 microM) stimulated the cAMP-dependent protein kinase in membranes, 38 +/- 7%, 31 +/- 6%, and 30 +/- 6%, respectively. Maximal stimulation of membrane protein kinase by 10 microM (-)epinephrine was obtained approximately equal to 30 min after initiation of the incubation of erythrocytes with the hormone. The concentrations of (-)catecholamines that gave half-maximal stimulation of the membrane protein kinase were 0.17 microM for isoproterenol, 0.35 microM for epinephrine, and 0.63 microM for norepinephrine. The membrane protein kinase response to beta-adrenergic agonists was found to be stereospecific. The stimulation of membrane protein kinase by 10 microM (-)epinephrine was inhibited by the beta-adrenergic antagonist, (-)propranolol with EC50 = 0.60 microM, and the inhibition of agonist stimulation of the cAMP-dependent protein kinase by propranolol was stereospecific. These studies suggest that a functional beta-adrenergic receptor exists in the mature human erythrocyte.
...
PMID:Catecholamine regulation of human erythrocyte membrane protein kinase. 22 12

The rat cerebellum contains a significant amount of cGMP-dependent protein kinase, cAMP-dependent and cyclic nucleotide-independent protein kinase, and a large concentration of protein kinase inhibitors. These inhibitors are thermostable proteins which can be separated by gel chromatography into two molecular forms: the type 1 and type 2 inhibitors of protein kinase (14). The type 1 inhibitor blocks the rat cerebellar cAMP-dependent protein kinase activity while the type 2 inhibitor blocks the cGMP-dependent protein kinase, the cAMP-dependent protein kinase, and the cyclic nucleotide-independent protein kinases. The activity of the type 2 inhibitor increased or decreased in opposite direction to changes of cerebellar cGMP content generated by injection of 10 mg/kg harmaline 2.5 mg diazepam. No changes of type 1 inhibitor were observed under these conditions. The drug-induced shift of type 2 inhibitor of protein kinase was not mediated by changes in protein synthesis because it persisted after pretreatment with cycloheximide. These results are compatible with the hypothesis that cGMP modulates phosphorylation in cerebellum by changing the relationship between cGMP-dependent protein kinase and type 2 inhibitor content.
...
PMID:Action of harmaline and diazepam on the cerebellar content of cyclic GMP and on the activities of two endogenous inhibitors of protein kinase. 22 76

Studies on the gonadotrophin-responsive adenylyl cyclase (AC) system of rabbit and porcine ovarian follicles reveal that hCG or LH-induced desensitization of the AC system can be divided into two phases: an initial, LH-specific phase and a second phase which is not specific for LH. The first phase occurs within the first hour after LH-hCG-receptor interaction, is agonist specific, and is not mediated by protein synthetic events or by cAMP. In view of our previous demonstration of the critical dependence of the LH-induced desensitizing process in cell-free membrane preparations of porcine follicles upon Mg2+ and ATP, we investigated the role of a phosphorylation reaction in the first phase of the AC desensitizing process. Porcine follicular membranes rich in LH-sensitive AC activity were found to contain the molecular requirements necessary for a phosphorylation reaction: namely, cAMP-dependent and cAMP-independent protein kinases as well as phosphoprotein phosphatases. The following lines of indirect evidence indicated that reversal or resensitization of the desenzitized AC system to LH was mediated by a dephosphorylation reaction. Activators of endogenous phosphoprotein phosphatases--Mn2+ and dithiothreitol--promoted a specific resensitization of the follicular AC system to LH. Likewise, a partially purified phosphoprotein phosphatase also resensitized the desensitized, LH unresponsive AC to LH, and boiling of the phosphatase prevented its effect. LH-induced desensitization of the AC system, on the other hand, did not appear to be mediated by a cAMP-dependent protein kinase, as evidenced both by the inability of beef heart protein to promote desensitization of AC and by the inability of an inhibitor of cAMP-dependent protein kinase to prevent LH-induced densensitization. The second phase of desensitization, which occurs after the first hour following hCG-LH-receptor interaction, is characterized by a loss of responsiveness to FSH as well as to LH and can be promoted by dibutryl cAMP (in the absence of LH). These results provide new evidence on the characteristics and molecular mechanism of LH-induced densensitization of the follicular AC system. These results indicate that the level of phosphorylation of membrane-associated components may, in part, regulate the activity of the AC system during this first phase of homologous desensitization.
...
PMID:LH-induced desensitization of the adenylyl cyclase system in ovarian follicles. 22 90

A system of translational control in eukaryotes consists of (a) a proinhibitor and (b) an inhibitor of polypeptide chain initiation. The inhibitor (active eIF-2 kinase), a cAMP-independent protein kinase, catalyzes the phosphorylation by ATP of the small subunit of the polypeptide chain initiation factor eIF-2. This blocks the interaction of eIF-2 with eIF-2 stimulating protein (ESP) without which eIF-2 is unable to form an initiation complex, a prerequisite for translation. Our observations are consistent with the view that the proinhibitor (inactive eIF-2 kinase) is converted to the inhibitor by phosphorylation catalyzed by a cAMP-dependent protein kinase. This is analogous to the conversion of inactive phosphorylase kinase to active phosphorylase kinase. As in the case of phosphorylase kinase and phosphorylase, the modification of activity produced by phosphorylation of eIF-2 kinase and eIF-2 itself is probably reversed by dephosphorylation catalyzed by specific protein phosphatases (see diagram in Fig. 12) but no evidence bearing on this aspect of the problem is yet available. Hemin inhibits the cAMP-induced dissociation of the regulatory and catalytic subunits of cAMP-dependent protein kinase by binding to the regulatory subunit of the enzyme and blocking, through an allosteric effect, the binding of cAMP. Thus, hemin prevents the activation of eIF-2 kinase by inhibiting the cAMP-dependent protein kinase.
...
PMID:Regulation of protein synthesis. 22 49

Two cAMP-dependent protein kinase activities can be separated from rat thyroid cytosol. Their elution properties during the gel chromatography, as well as their sedimentation coefficients after sucrose-gradient ultracentrifugation and their capacity to dissociate in the presence of histones, suggest they are like the Type I and Type II protein kinases described in many other tissues. The sensitivity of the two types of kinases to thyroxine treatment is different. The activity of Type I is not changed during the first 5 days of treatment. Thereafter, it decreased by about 50% and is maintained at that level for up to one month. The activity of the Type II enzyme decreased rapidly by about 30-40% already on the second day of treatment, and after 10 days it reached 50% of the initial level. This differential reactivity of the two types of enzymes to the thyroxine treatment leads to profound modifications in their relative activities between the second and the fifth day of treatment. The significance of these results and the possible role of the two types of kinases in the control of different steps of iodine metabolism have been discussed.
...
PMID:Hormonal regulation of thyroidal protein phosphokinase activities. II. Differential sensitivity of type I and type II cAMP-dependent enzymes to the treatment of rats with thyroxine. 22


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

---