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)

Despite the extensive literature on the biological actions of Ca2+ and calmodulin, very little is known about their involvement in nuclear functions, e.g., regulation of specific gene expression. To date, the only genes other than prolactin and growth hormone shown to be regulated by perturbations in cell Ca2+ are those coding for two glucose-regulated proteins. However, there is a growing body of indirect evidence for nuclear functions of Ca2+ and calmodulin, and we suspect that other examples of Ca2+-regulated genes will emerge. We have described in this chapter several different experimental approaches which we have employed to examine first whether prolactin gene expression is regulated by changes in cell Ca2+ content, and then to begin searching for the components of the mechanism by which Ca2+ exerts its effects on the prolactin gene. The tentative identification of 56-kDa nuclear matrix protein as both a calmodulin-binding protein and a substrate of a Ca2+-calmodulin-dependent protein kinase suggests that NMP 56 may be a subunit of a multifunctional Ca2+-calmodulin-protein kinase. This enzyme was recently detected in the nuclear matrix fraction of neuronal nuclei, and was shown to phosphorylate a chromatin protein similar to high mobility group protein 17 (HMG 17). Since HMG 17 is associated with actively transcribed chromatin, its phosphorylation in GH3 cells might play a role in the Ca2+-calmodulin-dependent regulation of prolactin gene expression by hormones and growth factors.
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PMID:Ca2+/calmodulin regulation of prolactin gene expression. 358 41

The acute anti-lipolytic effect of human growth hormone (hGH) in maximally noradrenaline-stimulated intact rat adipocytes was selectively associated with increased phosphorylation of a 46 kDa plasma membrane protein which was highly enriched by hGH-Sepharose chromatography. The same protein was also phosphorylated by an endogenous protein kinase in isolated plasma membranes, although then no hGH effect could be demonstrated. About 14% of the phosphate incorporated into the protein in isolated plasma membranes was found in tyrosine residues and the remainder in serine and threonine. The possible relation of the 46 kDa protein with the hGH plasma membrane receptor is discussed.
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PMID:The acute GH action in rat adipocytes is associated with enhanced phosphorylation of a 46 kDa plasma membrane protein enriched by GH-Sepharose. 378 Sep 67

The results of this communication show that ovine growth hormone (oGH) contains organically-bound phosphorous. The phosphorous content of growth hormone, lot S-11, is 1:3 (mol/mol) and that of lot S-12 is 1:6 (mol/mol). Results of 31P NMR studies suggest that the phosphorous exists in two chemical forms: as a monophosphoryl ester and as a phosphodiester. Evidence is provided which demonstrates that growth hormone can be phosphorylated in vitro with the catalytic subunit of protein kinase.
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PMID:Naturally-occurring pituitary growth hormone is phosphorylated. 399 21

The effect of phorbol diester tumour promoters on the release of growth hormone (GH) and prolactin (Prl) was studied in rat pituitary cells cultured in monolayer. 12-O-tetradecanoyl phorbol-13-acetate (TPA), the most potent phorbol ester, stimulated GH accumulation in the cultured medium in a dose-dependent manner. TPA also stimulated Prl accumulation. A time course study indicated that TPA mainly stimulates release of GH. The maximal stimulation of GH release by TPA (100 ng/ml) was 3-4-fold over control. Phorbol-12,13-dibutyrate (PDB), another tumour-promoting phorbol ester, stimulated GH release to an extent similar to that of TPA, while a biologically inactive compound, phorbol-12,13-diacetate (PDA), had no effect. TPA-stimulated GH release was not affected by the presence of indomethacin, an inhibitor of prostaglandin (PG) synthesis, indicating that PG is not involved in the process of TPA-stimulated GH release. Co++, a competitive antagonist of Ca++, at 2.0 mM completely suppressed the GH release induced by TPA, and this inhibition was partially reversed by the addition of 2.0 mM Ca++. Verapamil, a Ca++ channel blocker, reduced TPA-stimulated GH release, and trifluoperazine, an inhibitor of Ca-calmodulin formation, had a similar effect. Somatostatin (SRIF) also inhibited the GH release by TPA. These observations are compatible with the idea that Ca++ may be involved in the process of TPA-stimulated GH release. Since TPA has been reported to activate a Ca++- and phospholipid-dependent protein kinase (protein kinase C), it is possible that TPA stimulate GH release by activating the enzyme. Further studies are required to clarify this point.
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PMID:Effect of phorbol esters on the release of growth hormone and prolactin from rat pituitary cells cultured in monolayer. 614 63

The objective of this work was to identify the natural substrates of cyclic AMP-dependent protein kinase in pituitary cells. Studies were performed using 2 systems: intact pituitary cells stimulated with dibutyryl cyclic AMP (DBC) after preincubation with [gamma-32P]. Phosphorylation of proteins was analyzed by two-dimensional gel electrophoresis, followed by autoradiography. In intact cells, the only clear and reproducible effect of DBC stimulation is increased phosphorylation of 3 proteins (termed A, B, and C), each with a molecular weight of about 20 000 dalton. The time-course and dose-dependence of phosphorylation of A, B and C are generally similar to that for DBC-induced hormone secretion, which is consistent with a role for these proteins in the secretory mechanism. When [gamma-32P]ATP is added to cell extracts, proteins A, B, and C are not measurably phosphorylated, either in the absence or presence of cyclic AMP. This observation suggests that proteins A, B and C may not be directly phosphorylated by cyclic AMP-dependent protein kinase, but may be phosphorylated indirectly by a second kinase. On the other hand, growth hormone and prolactin are readily phosphorylated in cell extracts by cyclic AMP-dependent protein kinase (although they are not phosphorylated in vivo). This finding makes clear the need for caution in interpreting results from broke cell systems.
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PMID:Dibutyryl cyclic AMP-induced phosphorylation of specific proteins in adenohypophysial cells. 626

The molecular mechanism of growth hormone release by synthetic somatocrinin was investigated on purified hog anterior pituitary secretory granules; the granules were found to contain a cAMP-dependent protein kinase that catalyzed [gamma-32P]-ATP histone phosphorylation with maximal rates ranging from 1 to 5 nmol of Pi incorporated per mg of protein per 20 min. The activity of this enzyme was further stimulated by somatocrinin. Stimulation was observed at concentrations as low as 0.3 pM, and the half-maximal effect was obtained with 35 +/- 8 pM (n = 4). Michaelis-Menten analysis of phosphorylation kinetics suggested that the peptide did not change significantly the reaction's Vmax, but produced a dramatic increase in enzyme affinity for cAMP: the apparent Km for the nucleotide decreased from 400 X 10(-9) M under unstimulated conditions to 15 X 10(-9) M in the presence of 100 pM somatocrinin. Furthermore, a Hill plot of concentration-dependence curve indicated the existence of negative cooperativity. At the concentration of 35 pM, the less potent analogs of somatocrinin [designated hpGRF-44 to indicate source (human pancreas, hp), activity (growth hormone-releasing factor, GRF), and amino acid composition], hpGRF-(1-37) and [Phe1]hpGRF-(1-40) had 20% and 7%, respectively, of the effect of somatocrinin. The biologically inactive analog hpGRF-(2-40) had no evident effect at concentrations up to 0.1 microM. Therefore, we suggest that somatocrinin stimulation of growth hormone release involves activation of exocytosis through a phosphorylation mechanism mediated by a granular receptor coupled with a cAMP-dependent protein kinase.
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PMID:Somatocrinin receptor coupled with cAMP-dependent protein kinase on anterior pituitary granules. 631 30

This study shows that the growth hormone hypothalamic releasing factor (somatocrinin) stimulates the activity of cyclic AMP-dependent protein kinase associated with a purified fraction of hog anterior pituitary secretory granules. Threshold, half-maximal and maximal concentrations (0.3, 35 pM and 10 nM, respectively, in the presence of 50 nM cyclic AMP) are similar to those observed for in vitro stimulation of growth hormone release by somatocrinin.
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PMID:[Increase by somatocrinin of a cyclic AMP-dependent protein kinase activity in adenohypophyseal, secretory granules in the hog]. 631 26

We have investigated the ability of a constitutively active Gq-alpha mutant, Q209L-alpha q, to regulate target gene expression. Transient expression in GH3 pituitary cells of a rat proximal prolactin promoter-chloramphenicol acetyltransferase construct (-187)PRL-CAT, was stimulated by co-expression of Q209L alpha q, but not by wild-type alpha q. Q209L-alpha q stimulated expression of constructs driven by promoters for either rat prolactin or growth hormone, but not of a control construct driven by the thymidine kinase promoter. Thus, transcriptional effects of alpha q are specific both for the activated state of this G-alpha subunit and the promoter examined. Since both the prolactin and growth hormone promoters are activated by the pituitary cell-specific transcription factor Pit-1, we examined whether a Pit-1 binding site could direct a response to Q209L-alpha q. Two copies of prolactin promoter Pit-1 binding site 1P conferred upon a heterologous metallothionein promoter a response to Q209L-alpha q, implying an involvement of this site in the transcriptional action of Q209L-alpha q on the prolactin promoter. The phorbol ester activator of protein kinase C, 12-O-tetradecanoylphorbol-13-acetate, stimulated (-187)PRL-CAT activity, but opposed the action of Q209L-alpha q on activity of this PRL-CAT construct. Q209L-alpha q stimulation of (-187)PRL-CAT activity was inhibited by co-expression of a dominant negative Raf mutant, Raf-C4, but not by a point mutant of Raf-C4 with reduced inhibitory properties. These results imply that activated alpha q subunits can stimulate prolactin promoter activity via a pathway that involves a Pit-1 DNA binding site(s), is opposed by protein kinase C, and is mediated by a pathway in which Raf-1 kinase plays a role.
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PMID:Constitutively active Gq-alpha stimulates prolactin promoter activity via a pathway involving Raf activity. 748 29

Previously, we have demonstrated that dopamine (DA) stimulates growth hormone (GH) release from the goldfish pituitary through DA D1 receptors. In the present study, the role of cAMP in DA D1-stimulated GH release was investigated using static incubation of goldfish pituitary cells. The D1 agonist SKF38393 (1 nM-10 microM) induced GH release and cAMP accumulation in a dose-dependent manner with ED50s of 73 +/- 32 and 109 +/- 53 nM, respectively. In contrast, the D2 agonist LY171555 (1 nM-10 microM) was not effective in these regards. The GH-releasing action of SKF38393 was mimicked by the adenylate cyclase activator forskolin (0.1-40 microM) as well as the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.1 microM-1 mM). Dideoxyforskolin (0.1-40 microM), a derivative of forskolin inactive in stimulating adenylate cyclase, did not affect basal GH secretion. Similar stimulatory effects on GH release were also observed using the membrane-permeant cAMP analogs (10 microM-2 mM), dibutyryl cAMP and 8-bromo cAMP (8Br.cAMP). In the presence of a high dose (1 mM) of Br.cAMP, the ability of SKF38393 (1 nM-10 microM) to stimulate GH release was abolished, suggesting that the GH-releasing actions of cAMP and DA D1 stimulation are mediated through a common signal transduction mechanism. In the present study, the possible involvement of the cAMP-dependent enzyme protein kinase A (PKA) in DA D1-stimulated GH release was also examined. The GH responses to 8Br.cAMP (1 mM) and SKF38393 (1 microM) were blocked by simultaneous treatment with the PKA inhibitor H89 (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic 3',5'-adenosine monophosphate mediates dopamine D1-stimulated growth hormone release from goldfish pituitary cells. 752 99

To investigate whether alpha (alpha)-adrenoceptor agonists have a stimulatory effect on the expression of the angiotensinogen (Ang) gene in opossum kidney (OK) cells, we used OK 27 cells with a fusion gene containing the 5'-flanking regulatory sequence of the rat angiotensinogen gene fused with a human growth hormone (hGH) gene as a reporter, pOGH (Ang N-1498/+18), permanently integrated into their genomes. The level of expression of the pOGH (Ang N-1498/+18) was quantitated by the amount of immunoreactive-human growth hormone (IR-hGH) secreted into the medium. The addition of iodoclonidine (alpha 2-adrenoceptor agonist, 10(-13) to 10(-9) M) and phorbol 12-myristate 13-acetate (PMA, 10(-13) to 10(-5) M) stimulated the expression of pOGH (Ang N-1498/+18) in a dose-dependent manner, whereas the addition of phenylephrine (alpha 1-adrenoceptor agonist, 10(-13) to 10(-5) M) had no effect. The stimulatory effect of iodoclonidine was blocked by the presence of yohimbine (alpha 2-adrenoceptor antagonist) and staurosporine (an inhibitor of protein kinase C) but not blocked by the presence of prazosin (alpha 1-adrenoceptor antagonist) or Rp-cAMP (an inhibitor of cAMP-dependent protein kinase A). The addition of iodoclonidine, phenylephrine or PMA had no effect on the expression of pTKGH in OK 13 cells, an OK cell line, into which had been stably integrated a fusion gene, pTKGH containing the promoter/enhancer DNA sequence of the viral thymidine-kinase (TK) gene fused with a human growth hormone gene as a reporter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-adrenoceptors and angiotensinogen gene expression in opossum kidney cells. 756 70


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