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

Hypothalamic proTRH mRNA levels are rapidly increased (at 1 h) in vivo by cold exposure or suckling, and in vitro by 8Br-cAMP or glucocorticoids. The aim of this work was to study whether these effects occurred at the transcriptional level. Hypothalamic cells transfected with rat TRH promoter (-776/+85) linked to the luciferase reporter showed increased transcription by protein kinase (PK) A and PKC activators, or by dexamethasone (dex), but co-incubation with dex and 8Br-cAMP decreased their stimulatory effect (as observed for proTRH mRNA levels). These effects were also observed in NIH-3T3-transfected cells supporting a characteristic of TRH promoter and not of hypothalamic cells. Transcriptional regulation by 8Br-cAMP was mimicked by noradrenaline which increased proTRH mRNA levels, but not in the presence of dex. PKA inhibition by H89 avoided 8Br-cAMP or noradrenaline stimulation. TRH promoter sequences, cAMP response element (CRE)-like (-101/-94 and -59/-52) and glucocorticoid response element (GRE) half-site (-210/-205), were analyzed by electrophoretic mobility shift assays with nuclear extracts from hypothalamic or neuroblastoma cultures. PKA stimulation increased binding to CRE (-101/-94) but not to CRE (-59/-52); dex or 12-O-tetradecanoylphorbol-13-acetate (TPA) increased binding to GRE, a composite site flanked by a perfect and an imperfect activator protein (AP-1) site in the complementary strand. Interference was observed in the binding of CRE or GRE with nuclear extracts from cells co-incubated for 3 h with 8Br-cAMP and dex; from cells incubated for 1 h, only the binding to GRE showed interference. Rapid cross-talk of glucocorticoids with PKA signaling pathways regulating TRH transcription constitutes another example of neuroendocrine integration.
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PMID:Dexamethasone represses cAMP rapid upregulation of TRH gene transcription: identification of a composite glucocorticoid response element and a cAMP response element in TRH promoter. 1569 87

The mechanisms of paradoxical TRH response in human somatotroph adenoma cells were investigated using intracellular calcium measurement and static incubation assay. Intracellular calcium measurement revealed that TRH induces a biphasic response: a transient increase followed by a sustained plateau. The transient phase was due to the calcium release from IP(3)-regulated intracellular calcium store and the subsequent sustained phase was due to the calcium influx through the voltage-gated calcium channels. The signal transduction mechanism of the calcium plateau involved protein kinase C. These calcium responses, especially the second phase, was responsible for the TRH-induced GH release.
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PMID:Mechanisms of TRH-induced GH release (paradoxical response) in human somatotroph adenoma cells. 1641 Jun 70

Thyroid hormones play critical roles in differentiation, growth and metabolism, but their participation in immune system regulation has not been completely elucidated. Modulation of in vivo thyroid status was used to carry out an integrative analysis of the role of the hypothalamus-pituitary-thyroid (HPT) axis in T and B lymphocyte activity. The participation of the protein kinase C (PKC) signaling pathway and the release of some cytokines upon antigenic stimulation were analyzed. Lymphocytes from hyperthyroid mice displayed higher T-and B-cell mitogen-induced proliferation, and those from hypothyroid mice displayed lower T- and B-cell mitogen-induced proliferation, compared with euthyroid animals. Reversion of hypothyroid state by triiodothyronine (T3) administration recovered the proliferative responses. No differences were found in lymphoid subset balance. Both total PKC content and mitogen-induced PKC translocation were higher in T and B cells from hyperthyroid mice, and lower in cells from hypothyroid mice, compared with controls. Levels of thyroid-stimulating (TSH) and TSH-releasing (TRH) hormones were not directly related to lymphocyte proliferative responses. After immunization with sheep red blood cells (SRBCs) and re-stimulation, in vitro spleen cells from hyper- or hypothyroid mice showed, respectively, increased or decreased production of interleukin (IL)-2 and interferon (IFN)-gamma cytokines. Additionally, an increase in IL-6 and IFN-gamma levels was found in hyperthyroid cells after in vivo injection and in vitro re-stimulation with lipopolysaccharide (LPS). Our results show for the first time a thyroid hormone-mediated regulation of PKC content and of cytokine production in lymphocytes; this regulation could be involved in the altered responsiveness to mitogen-induced proliferation of T and B cells. The results also confirm the important role that these hormones play in regulating lymphocyte reactivity.
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PMID:Integrative study of hypothalamus-pituitary-thyroid-immune system interaction: thyroid hormone-mediated modulation of lymphocyte activity through the protein kinase C signaling pathway. 1661 80

Biosynthesis of TRH, a neuropeptide involved in energy homeostasis, is modulated by glucocorticoids. TRH mRNA and peptide levels are increased upon incubation of hypothalamic cells with dexamethasone or with cAMP analogs but when combined, a mutual antagonism is observed. These effects are observed at the transcriptional level and on binding of glucocorticoid receptor (GR) or pCREB to the composite GRE (cGRE) and CRE-2 sites of TRH promoter. The present work studied the involvement of PKC and MAPK pathways on the effect of dexamethasone and on its interaction with cAMP signaling in hypothalamic cell cultures. PKC or MEK inhibition abolished dexamethasone-stimulatory effect on TRH mRNA levels, as well as its interference with the stimulatory effect of 8Br-cAMP. Binding of nuclear extracts from hypothalamic or neuroblastoma cells stimulated with dexamethasone or 8Br-cAMP to oligonucleotides containing the CRE or cGRE sites of TRH gene promoter was decreased if cells were preincubated with PKC or MEK inhibitors. Mutations on the AP-1 or the GRE half sites of cGRE showed that GR binds as an heterodimer on cGRE, and PKC or MEK inhibitors diminish binding at the AP-1 site. PKC and ERK signaling thus modulate GR activity and its interaction with CREB or AP-1 at the TRH gene promoter.
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PMID:The PKC and ERK/MAPK pathways regulate glucocorticoid action on TRH transcription. 1842 88

Abstract Protein kinase C was activated in Xenopus laevis oocytes by phorbol ester treatment and its effects on the inositol trisphosphate/Ca(2+) transmembrane signalling pathway analysed. Induction of the pathway was achieved by ligand stimulation of TRH receptors translated from GH(3) pituitary cell mRNA. In voltage-clamped oocytes bath application of peptide, injection of guanosine 5'-(3-O-thio) triphosphate (GTPgammaS), inositol trisphosphate or Ca(2+) all elicited inward membrane currents. Treatment of oocytes with tumour-promoting phorbol esters for 35 min almost completely abolished the ligand and GTPgammaS-induced responses. In contrast, phorbol ester treatment enhanced inositol trisphosphate-generated membrane currents. Ca(2+)-mediated responses remained unaffected by tumour promoters. The data indicate a dual role for protein kinase C in the modulation of transmembrane signalling: a feedback mechanism prevents phosphoinositide turnover whereas a feedforward reaction triggers the effect of intracellular inositol trisphosphate on the Ca(2+) release.
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PMID:Modulation of Neuropeptide-lnduced Membrane Currents by Protein Kinase C in Xenopus Oocytes Injected with GH Pituitary Cell Poly(A) RNA. 1921 Apr 84

Angiotensin II (AII) and thyreoliberin (TRH) have recently been shown to stimulate intracellular cAMP formation in rat lactotroph cells, in addition to their already documented coupling to phospholipase C. The effect on intracellular cAMP is unaffected by pertussis toxin (PTX) and is not due to a direct coupling to adenylate cyclase (AC); it results instead from a protein kinase C (PKC)-dependent process. In contrast, when tested in membrane preparations, AII, but not TRH, induces a PTX-sensitive inhibition of AC. The present work indicates that AII, but not TRH, is also able to inhibit intracellular cAMP formation in mixed as well as in lactotroph-enriched cells. Two conditions are required to reveal this effect: desensitization of PKC by prior exposure to TPA and concomitant stimulation of CAMP level. This effect is observed only in the presence of vasoactive intestinal peptide, whose receptor is directly coupled to AC, but not in the presence of other AC-stimulating agents such as cholera toxin and forskolin. This AII inhibitory effect is dose dependent and sensitive to PTX as is AII membrane inhibition of AC activity. PTX also reverses DA inhibition of AC, on both membrane preparations and intact cells. However different G proteins seem to be involved in the negative coupling of AII and DA receptors, since both effects do not exhibit the same PKC sensitivity in entire cells and GTP dependency in membrane preparations. An inhibitory coupling of the AII receptor with AC thus exists in intact cells but is masked by PKC interactions. Under specific conditions, this AII inhibition of intracellular cAMP formation might be implicated in the regulation of PRL secretion.
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PMID:PKC modulation of inhibitory coupling of angiotensin II receptors with adenylate cyclase in lactotroph cells. 1991 54


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