Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (somatotropin) is a potent anabolic protein currently being evaluated clinically in cachexia associated with malignancy and human immunodeficiency virus (HIV) disease. Growth hormone can also lead to enhancement of lectin-mediated cellular proliferation, macrophage activation, and cytokine induction, events linked to induction of latent HIV in vitro. We thus explored the ability of recombinant human growth hormone (rhGH) to affect viral replication in acute and chronic HIV infection, and to alter transcription at the HIV-1 long terminal repeat (LTR). A clone of promonocytic cells, chronically infected with HIV-1 and susceptible to viral induction by a variety of cytokines and protein kinase C activators, was unperturbed by rhGH used over broad concentrations (10 to 500 ng/mL) and time intervals. This unresponsiveness paralleled the lack of effect of rhGH on HIV-associated trans-activation in both monocytic and CD4+ T-cell lines. In contrast, rhGH enhanced viral replication in acutely infected peripheral blood mononuclear cells (PBMC) by twofold to 20-fold, albeit having no adverse effect on the antiviral efficacy of zidovudine (AZT). Augmentation of HIV growth correlated with stimulation of cellular DNA synthetic responses and an increase in tumor necrosis factor-alpha (TNF-alpha) secretion. These data are discussed in the context of ongoing clinical trials of rhGH in HIV-seropositive individuals with wasting syndromes.
 ...
PMID:Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro. 173 91

A direct and modulating effect of growth hormone (GH) on the regulation of the lipoprotein lipase (LPL) gene has been shown in preadipocyte Ob1771 cells. Growth hormone acts as a modulator within the physiological range of concentrations and regulates the abundance of the two species of LPL mRNAs (3.3 and 3.7 kb) in a differentiation-dependent manner, the stimulation factor being between 4- and 7-fold. The regulation of LPL gene expression by GH is rapid (2 to 8 h) and similar for both mRNA species. It is reversible and takes place primarily at a transcriptional level. Parallel increases of LPL mRNAs, LPL protein, and LPL activity are observed. The expression of both cellular and secreted activities is stimulated by GH. The role of GH is mediated, at least in part, by means of activation of protein kinase C. In the presence of 4-beta-phorbol-12-myristate 13-acetate (PMA), a parallel increase of LPL mRNA content and LPL activity is observed at half the values obtained upon stimulation by GH. The kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) abolishes completely the PMA-induced accumulation but decreases only by half that induced by GH. Like H7, staurosporine, polymixin B, and sphingosine inhibit only by half the stimulatory effect of GH on the expression of the LPL gene. These results show for the first time a rapid regulation of the LPL gene expression at a transcriptional level. Ob1771 cells should be helpful in gaining some insights in the promoter function of the LPL gene and the trans-acting factors involved in its regulation.
 ...
PMID:Transcriptional control of the expression of lipoprotein lipase gene by growth hormone in preadipocyte Ob1771 cells. 240 59

Growth hormone (GH) is required for the terminal differentiation of preadipose Ob1771 cells that have entered the differentiation program as evidenced by the expression of early marker genes (pOb24 and lipoprotein lipase). Induction of c-fos mRNA within 15 min and induction of insulin-like growth factor I mRNA within a few hours take place in response to GH. The role of GH is mediated, at least in part, by means of the activation of protein kinase C, as shown by the inhibition of epidermal growth factor binding and by the expression of the c-fos gene, and is thus analogous to the action of prostaglandin F2 alpha and 4 beta-phorbol-12,13-didecanoate in this respect. However, in contrast to that of the c-fos gene, the regulation of insulin-like growth factor I gene expression by GH is not mediated by means of the activation of protein kinase C, and, in line with this, prostaglandin F2 alpha and 4 beta-phorbol-12,13-didecanoate were ineffective. GH and prostaglandin F2 alpha were able to stimulate the formation of diacyglycerol within a few seconds, but GH did not elicit an accumulation of inositol phosphates, in contrast to that generated by prostaglandin F2 alpha. We conclude that the transduction signal of GH action in c-fos mRNA induction is the formation of diacylglycerol and that the mechanism whereby GH can activate protein kinase C is associated with a phospholipase C-mediated hydrolysis of glycerophospholipids other than inositol phospholipids.
 ...
PMID:Growth hormone stimulates c-fos gene expression by means of protein kinase C without increasing inositol lipid turnover. 249 51

Growth hormone releasing peptide (GHRP-6) is a synthetic hexapeptide which specifically stimulates secretion of growth hormone (GH) by pituitary somatotrophs. The precise intracellular mechanism by which this is achieved has not been deciphered although it is known to involve protein kinase C (PKC) and Ca2+ but to be cAMP-independent. We have used cell cultures of human pituitary somatotrophinomas to demonstrate powerful effects of GHRP-6 on membrane phosphatidylinositol (PI) turnover, a second messenger system which leads to activation of PKC and mobilisation of intracellular Ca2+ reserves. Incubation of somatotrophinoma cells with GHRP-6 led to a dose-dependent stimulation of rate of PI turnover. GH secretion was increased in parallel. Effects were discernable after only 15 minutes incubation and rose to a maximum at 2 hours. PI turnover was stimulated by GHRP-6 in 8 of 8 tumours examined, effects ranging from 2.1 - 7.9 fold increases. Stimulation of GH secretion by GHRP-6 was independent of presence of gsp oncogenes, emphasising the cAMP-independent nature of its effects. These results provide evidence that the GH-stimulatory effects of GHRP-6 are achieved through activation of the PI second messenger system and thus support earlier findings that PKC and Ca2+ play central roles in mediating the effects of GHRP-6.
 ...
PMID:Growth hormone releasing peptide (GHRP-6) stimulates phosphatidylinositol (PI) turnover in human pituitary somatotroph cells. 777 38

Lipoprotein lipase (LPL) is known to be an early marker of adipose cell differentiation. Growth hormone (GH) stimulates in preadipose Ob1771 cells the expression of LPL gene and this effect is mediated at least in part by c-fos protooncogene, the expression of which is transiently activated by a protein kinase C-dependent pathway (Barcellini-Couget et al., Endocrinology, 1993, 132: 55-60). Since GH stimulates the formation of diacylglycerol from phosphatidylcholine independently of Ca2+ mobilization, the role of Ca2+ was studied in regard to LPL gene expression stimulated by GH. The results obtained in the presence of Ca2+ ionophores show that a rise in intracellular free Ca2+ abolishes this expression but has no effect on the expression of various adipose-related genes, including the transient expression of c-fos protooncogene. Therefore, the inability of preadipose cells to mobilize Ca2+ in response to GH, at an early stage of the differentiation process, appears as a prerequisite for the maximal expression of LPL.
 ...
PMID:Rise in cytosolic Ca2+ abolishes in preadipose cells the expression of lipoprotein lipase stimulated by growth hormone. 812 5

Growth hormone (GH) is an important regulator of the expression of several members of the cytochrome P4502C subfamily in rat liver. The sexually differentiated pattern of secretion of GH in the adult rat leads to a sex-dependent expression of the GH-regulated P450 genes. The continuous presence of GH in serum is characteristic of the female rat and maintains a high expression of P4502C12 while it represses P4502C11 expression. By contrast, the P4502C11 form is induced by the intermittent, male characteristic, GH pattern. A direct effect of GH on the hepatocyte is evident from studies using primary adult rat hepatocytes in culture and, furthermore, the regulation has been shown to occur at the level of transcription. How the hepatocyte can distinguish between different patterns of GH exposure is as yet unresolved and neither are the signalling pathway(s) that are involved in the mediation of the GH effects known. However, a cascade of phosphorylations starting at the receptor are triggered. Our data indicate that protein kinase C activity is necessary for the GH effect on P4502C12 and that some other kinase, sensitive to staurosporine, is a determining transducer. The dual regulation by GH of the genes encoding P4502C11 and P4502C12 and the GH responsiveness of primary hepatocytes offer versatile tools for studies aimed at understanding the cellular and molecular mechanisms of GH action.
 ...
PMID:Sexually differentiated expression of genes encoding the P4502C cytochromes in rat liver--a model system for studying the action of growth hormone. 831 17

Growth hormone promotes the differentiation of 3T3-F442A preadipocytes via unknown mechanisms. The ability of growth hormone to enhance the phosphorylation of ribosomal protein S6 through the activation of S6 kinases in this cell line was investigated. Growth hormone rapidly stimulated an S6 phosphotransferase activity measured in unpurified extracts. Using specific antisera, this activity was resolved into two components, comprising the p90rsk and p70s6k S6 kinases. Activation of these enzymes occurred simultaneously within minutes but proceeded with distinct time courses. p90rsk activation was transient, down-regulating within 60 min, whereas p70s6k activation was sustained beyond this time. The degree of activation of both S6 kinases by growth hormone closely paralleled their apparent phosphorylation status, with multi-site phosphorylation associated with full activation. Pretreatment of cells with a selective inhibitor of protein kinase C prevented activation of both S6 kinases by growth hormone but not by epidermal growth factor.
 ...
PMID:Simultaneous activation of p90rsk and p70s6k S6 kinases by growth hormone in 3T3-F442A preadipocytes. 838 47

Growth hormone (GH) has been previously shown in Ob1771 adipose cells to transiently stimulate the expression of the c-fos gene by a protein kinase C (PKC)-dependent pathway. This regulation takes place at a transcriptional level. In the presence of cycloheximide (CHX), stimulation by PKC activators or by serum leads to a "superinduction" of the c-fos gene. In contrast, upon GH stimulation in the presence of CHX, no superinduction takes place and neither prolonged transcription nor mRNA stabilization are observed.
 ...
PMID:Regulation of c-fos proto-oncogene expression by growth hormone: protein synthesis is not required for down-regulation. 846 86

The regulation of clonal rat insulinoma (RINm5F) cell proliferation and hormone accumulation was investigated with the aim of identifying putative compounds capable of inducing differentiation, i.e. decreased growth and increased insulin accumulation, by the tumor cells. In particular, interest was focused on the role of a number of peptides as well as pharmacological probes modulating various signal transduction systems and which have been shown to regulate normal beta-cell proliferation and insulin accumulation. Growth hormone stimulated insulin accumulation and inhibited DNA synthesis, whereas galanin and insulin-like growth factor I caused a moderate suppression of insulin accumulation but did not affect proliferation, while epidermal growth factor, transforming growth factor beta, platelet-derived growth factor, acidic and basic fibroblast growth factor, bradykinin and somatostatin were virtually inactive on all parameters tested. Exogenous prostaglandins E2 and F1 alpha were inactive, while the cycloxygenase inhibitor indomethacin slightly suppressed insulin accumulation. The cytokine IL-1 beta caused a significant decrease in both beta-cell mitogenesis and insulin accumulation, effects that were mediated through nitric oxide generation. The vitamin A derivative retinyl acetate slightly inhibited serum-stimulated DNA synthesis, but did not affect insulin accumulation. The vitamin E alpha-tocopherol significantly enhanced insulin release but did not affect mitogenesis. By contrast, gamma-tocopherol was inactive on both these parameters. The alpha-adrenergic agonist clonidine evoked a slight inhibition of serum-stimulated DNA synthesis, without influencing insulin accumulation, whereas phenylephrine did not affect any of these parameters. Carbamylcholine increased insulin accumulation, but not cell proliferation, whereas the adenylyl cyclase activator forskolin suppressed mitogenesis but did not affect insulin accumulation. Inhibition of protein kinase C with staurosporine or prolonged treatment with phorbol ester suppressed DNA synthesis, as did the tyrosine kinase inhibitor genistein. Stimulating Ca2+ influx by closing ATP-dependent K+ channels with glibenclamide enhanced DNA synthesis, while opening of these channels with diazoxide suppressed cell growth. Conversely, preventing Ca2+ influx by the Ca2+ channel antagonist D-600, chelating intracellular Ca2+ by fura-2 AM or inhibiting the Ca2+/calmodulin-dependent protein kinase by calmidazol resulted in a decreased DNA synthesis. On the other hand, uncontrolled influx or mobilization of Ca2+ by ionomycin or thapsigargin resulted in an arrested DNA synthesis. The present paper shows that RINm5F insulinoma cell proliferation and insulin accumulation can be modulated by various peptidergic and pharmacological agents regulating certain signal transduction pathways. However, mitogenesis in the insulinoma cells seemingly is controlled in a vastly different manner in comparison to that in normal beta-cells. The most spectacular finding in this screening study, i.e. that growth hormone, contrarily to its effect on normal beta-cells, suppresses insulinoma cell growth, merits further elucidation of the underlying mechanisms. Possibly the hormone might become of utility in a clinical setting in the treatment of patients with insulin-producing tumors.
 ...
PMID:Regulation of insulinoma cell proliferation and insulin accumulation by peptides and second messengers. 880 83

Growth hormone (GH) has long been known to stimulate linear growth and regulate metabolism. The cellular mechanism by which GH elicits these effects has only recently begun to be understood. This review provides an overview of a current model of GH signaling. Briefly, binding of GH to GH receptor induces receptor dimerization and activation of the tyrosine kinase JAK2. Tyrosyl phosphorylation of GH receptor and JAK2 recruits and activates signaling molecules such as Stat transcription factors, SHC, and insulin receptor substrates 1 and 2 that lead to the release of second messengers such as diacylglycerol, calcium, and nitric oxide and the activation of enzymes such as mitogen-activated protein kinase, protein kinase C, phospholipase A2, and phosphatidylinositol 3'-kinase. These pathways regulate cellular function including gene transcription, metabolite transport, and enzymatic activity that result in the ability of GH to control body growth and metabolism.
 ...
PMID:Mechanism of signaling by growth hormone receptor. 887 95


1 2 3 Next >>