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

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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)

Pituitary adenylate-cyclase-activating peptide (PA-CAP) and PACAP-27 are novel hypothalamic peptides that can stimulate adenylate cyclase in cultured anterior pituitary cells. Because these peptides are present in the gut and are homologous with vasoactive intestinal peptide (VIP), itself known to stimulate intestinal ion transport, we examined the effects of these peptides on the T84 colonocyte cell line. Using cells grown on semipermeable supports and mounted in Ussing chambers, we showed that PACAP and PACAP-27 potently activate intestinal secretion. The half-maximal secretory response was produced with 0.5 nmol/L PA-CAP and 0.1 nmol/L PACAP-27. PACAP resembled VIP in that it stimulated a secretory response potentiated by carbachol, inhibited by bumetanide and barium chloride, and not further stimulated by the subsequent addition of VIP. Like VIP, PACAP also stimulated 5' cyclic adenosine monophosphate (cAMP) production and the phosphorylation of cellular proteins known to be substrates for cAMP-dependent protein kinase. In addition, PACAP inhibited 125I-VIP binding to T84 cells, and the secretion it stimulated was reduced by the VIP receptor antagonist, L-8-K. Thus PACAP and PACAP-27 potently stimulate colonocyte ion transport via mechanisms mediated by the VIP receptor and cAMP-dependent signaling.
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PMID:Pituitary adenylate cyclase-activating polypeptide stimulates secretion in T84 cells. 132 72

Pituitary lactotroph cell function and PRL gene expression are highly regulated by the cAMP-protein kinase-A (PKA) pathway. To further our understanding of the molecular mechanisms by which cAMP/PKA regulates rat (r) PRL promoter activity and to determine whether cAMP regulation is cell type specific, we 1) transected intact (-425), internal and 5'-deletion, and site-specific mutants of the rPRL promoter ligated to the firefly luciferase reporter gene into both pituitary and nonpituitary cell lines; and 2) assessed the role of the cAMP-cAMP response element-binding protein (CREB) pathway in GH4 rat pituitary cells. The data show that deleting the rPRL promoter from -425 to -116 did not abolish cAMP regulation, implying that proximal elements, such as the basal transcription element (-112/-80) or the pituitary-specific footprint (FP) I (-67/-45), mediate the cAMP response. However, nucleotide changes within FP I or FP II (-130/-120) did not alter the rPRL promoter response to 1 microM forskolin (FSK), despite the 77% and 26% reductions in basal rPRL promoter activity caused by these mutations, respectively. Furthermore, internal deletion of either the basal transcription element of FP I element also failed to affect cAMP regulation of the rPRL promoter, again despite the 90% and 93% reductions in basal promoter activity by these deletions, respectively. Since these internal deletion constructs otherwise contain rPRL promoter sequences from -425 to +73, including the up-stream pituitary-specific FPs III and IV, the data suggest that any one of these cell-specific elements is capable of imparting cAMP regulation to the proximal rPRL promoter. To directly test the implication that the cAMP response of the rPRL promoter is restricted to the pituitary-specific cell type, we took advantage of a 5'-deletion mutant truncated at position -116 and a FP II site-specific mutant, since constructs containing these rPRL promoters are active in nonpituitary cells. Despite the 6.6- and 18.5-fold stimulations over wild-type rPRL promoter activity in nonpituitary cells, respectively, these mutations remained completely unresponsive to FSK treatment. To document that the cAMP-CREB pathway was functional in GC/GH4 rat pituitary cells, CREB was affinity purified from GC rat pituitary cells, and DNase-I protection studies showed that it does not bind to the proximal rPRL promoter. Also, the human glycoprotein alpha-subunit promoter was induced 10-fold by FSK in GH4 rat pituitary cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cyclic adenosine 3',5'-monophosphate activation of the rat prolactin promoter is restricted to the pituitary-specific cell type. 133 42

Gonadotropes respond to GnRH with LH synthesis and release, desensitization, changes in GnRH receptor number, and GnRH receptor synthesis. Activation of protein kinase-C (PKC) appears to be involved in LH beta gene expression, but is not required for acute LH release, desensitization, or receptor down-regulation. The present studies were conducted to determine whether PKC mediates GnRH-stimulated receptor synthesis. We have adapted the density shift technique to measure the synthesis of GnRH receptors in pituitary culture. Pituitary cells from female weanling rats were exposed to medium containing treatments, dense amino acids (greater than 95% 13C, 15N, and 2H), dialyzed horse serum (10%, vol/vol), and fetal calf serum (2.5%, vol/vol). Treatments consisted of medium alone, phorbol myristate acetate (PMA), phorbol dibutyrate (PdBu), or GnRH. To deplete cells of PKC, cultures were exposed for 8-16 h to 1 microM PMA. Short term treatment with PKC activators (PMA or PdBu, 1 microM) or GnRH (0.1 nM) was given for 30 min. After treatment, GnRH receptors were covalently linked to [125I]Tyr5-azidobenzoyl-D-Lys6-GnRH and solubilized. Newly synthesized (densely labeled) GnRH receptors were separated from normal receptors by velocity sedimentation (156,000 X g; 24 h; 0-20% sucrose) and quantified by gamma-spectroscopy. Treatment with GnRH significantly stimulated the synthesis of GnRH receptors. Treatment of pituitary cell cultures with PMA (8-16 h) also stimulated the synthesis of GnRH receptors, although to a lesser extent than that observed after GnRH treatment. The synthesis of GnRH receptors in response to 0.1 nM GnRH was not different in cells with a normal complement of PKC compared to those depleted of PKC activity. This indicates that the ability of GnRH to stimulate the synthesis of its own receptor is not mediated by PKC. Short term treatment of cell cultures with 1 microM PMA or PdBu (30 min) stimulated GnRH receptor synthesis similar to treatment with 0.1 nM GnRH. When PMA and GnRH were administered simultaneously, GnRH receptor synthesis was stimulated to a greater extent than with either agent alone, suggesting differing mechanisms of action. These results indicate that although activators of PKC can stimulate the synthesis of GnRH receptors, PKC does not mediate the effects of GnRH on homologous receptor synthesis.
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PMID:Protein kinase-C activation stimulates synthesis of gonadotropin-releasing hormone (GnRH) receptors, but does not mediate GnRH-stimulated receptor synthesis. 165 76

The pituitary of goitrogen-treated White Leghorn cockerels is smaller in size than control birds and the pituitaries of castrated cockerels is nearly twice the size of control birds. The pituitary cells generated by these treatments may not be functional thyrotrophs or gonadotrophs and may not be able to respond to their usual stimuli. Low ambient temperature is a well-known stimulus to the thyroid gland acting through pituitary TSH. Cyclic-AMP-dependent protein kinase activity levels are used here as an index of cellular activity in the pituitary and thyroid glands. Castrated cockerels with or without methimazole treatment do not have an increased pituitary cAMP-dependent protein kinase activity in cold. Methimazole-treated birds have an exaggerated pituitary protein kinase response to cold stress when compared with controls. Pituitary cAMP-dependent protein kinase activity is paralleled by a similar activity increase in the thyroid gland of methimazole-treated cockerels and no increase in the thyroid of castrated birds. Castrated birds at all temperatures have an elevated thyroid cAMP-dependent protein kinase activity ratio which is interpreted as the result of removal of testosterone inhibition.
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PMID:The effects of castration and/or methimazole feeding on the pituitary response to temperature extremes by cockerels. 300 Aug 64

Phospholipid-dependent, Ca2+-activated protein kinase (C-kinase) was recently shown to be expressed in rat pituitary. The enzyme is activated by Ca2+ and phosphatidylserine (PS). Diacylglycerol (DG), which is liberated during phosphoinositide turnover, and the potent tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) activate pituitary C-kinase in the presence of PS, even at resting levels of intracellular Ca2+ (10(-7) M), and increase the apparent affinity of the enzyme for Ca2+. While micromolar concentration of Ca2+ had no effect on the apparent affinity of the enzyme for PS (Km approximately 15 micrograms/ml), elevation of Ca2+ to the millimolar range produced a sharp increase in the apparent affinity for PS (Km approximately 5 micrograms/ml). Elevation of PS (up to 500 micrograms/ml) could not replace Ca2+ in supporting maximal enzyme activity even in the presence of DG. Cytosolic pituitary C-kinase (70% of total enzyme activity) is recovered in an inactive state and can be activated without further purification. The particulate enzyme (30%) is recovered in a cofactors-insensitive form but can be activated after detergent-solubilization and anion exchange chromatography. Endogenous redistribution of soluble pituitary C-kinase to the membrane does not convert it to its proteolytic product which is insensitive to Ca2+, PS and DG. Pituitary C-kinase characterized here most likely plays a key role in signal transduction mechanisms involved in pituitary functions.
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PMID:Phospholipid-dependent Ca2+-activated protein kinase (C-kinase) in the pituitary: further characterization and endogenous redistribution. 375 74

We report the presence in the rat pituitary of a calcium-activated, phospholipid-dependent protein kinase (C kinase), originally described by Takai et al. [Takai, Y., Kishimoto, A., Iwasa, Y., Kawahara, Y., Mori, T. & Nishizuka, Y. (1979) J. Biol. Chem. 254, 3692-3695]. Enzyme activity is absolutely dependent on the simultaneous presence of Ca2+ and phospholipid--in particular, phosphatidylserine. The presence of small amounts of unsaturated diacylglycerol greatly increases the apparent affinity of the enzyme for Ca2+ and phosphatidylserine. Pituitary C kinase is mostly soluble (70%) and partly particulate (30%). Although the soluble form of the enzyme can be detected in a crude cytosol preparation, the particulate form is detectable only after solubilization and anion-exchange chromatography. Administration of a gonadotropin-releasing hormone (Gn-RH) agonist analog, [D-Ser(But)6]des-Gly10-Gn-RH-N-ethylamide, to ovariectomized rats resulted in elevated serum luteinizing hormone levels (245%) accompanied by a decrease in the cytosolic form of the enzyme (60%) and an increase in the particulate form (300%) after 5 min. This apparent activation of the particulate form seems to result from translocation of a soluble C kinase to the membrane. Several endogenous substrate proteins for C kinase ranging from 16 to 100 kDa were identified in pituitary cytosol. Pituitary C kinase might be involved in signal-transduction mechanisms in Gn-RH action, in particular, and in other hypophysiotropic hormones, in general, which operate by means of stimulation of phosphoinositide turnover during which diacylglycerol is liberated.
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PMID:Characterization of pituitary calcium-activated, phospholipid-dependent protein kinase: redistribution by gonadotropin-releasing hormone. 390 59

Pituitary cyclic adenosine monophosphate-dependent protein kinase (cAMP-PK) activity ratios of castrated cockerels on a short photoperiod are highest 2 weeks after testosterone removal in castrated birds and remain high through a 3rd week. Castrated cockerels on long photoperiods have a decline in cAMP-PK activity ratios after an elevation at 1 week following testosterone removal. This is interpreted to mean that the pituitaries of cockerels on short photoperiods are sensitive to testosterone inhibition but that this sensitivity disappears in long photoperiod-stimulated birds. Long daylengths also appear to enhance thyroid activity in castrated cockerels, although thyroid cAMP-PK activity ratios increase in the thyroid of all cockerels following the removal of testosterone (castration). These results suggest that testosterone has an inhibitory effect on both the pituitary and thyroid glands.
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PMID:Some effects of photoperiod on the pituitary/thyroid axis of castrated cockerels. 401 60

Pituitary cyclic AMP-dependent protein kinase (cAMP-PK) activity ratios are not increased in response to thyrotropin-releasing hormone (TRH) in old chickens (retired White Leghorn breeders). This reduced responsiveness may be due to reduced hypothalamic function, reduced thyrotrope function, or to a reduction in TRH membrane receptors. The thyroid cAMP-PK activity ratio of old males does not respond to TRH treatment but the thyroid of old females does have an increased activity ratio ater TRH injection. Both males and females have a much higher basal cAMP-PK activity ratio than young birds. This higher basal level is thought to be due to an increased thyroid-stimulating hormone (TSH) stimulation, and the failure of old males to increase activity after TRH injections may be due to a loss of the thyroid's ability to respond to direct TRH stimulation.
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PMID:Age-related changes in pituitary/thyroid function in chickens. 630 97

Pituitary regulation of reproductive processes depends on the sensitivity of gonadotrope cells to both positive and negative regulators. Hypothalamic GnRH is the primary stimulus for gonadotropin synthesis and secretion. Therefore, the ability of the gonadotrope to respond to GnRH and the status of GnRH receptors (GnRH-R) are critical in the control of reproduction. In the present study, we address the role of GnRH and two second messenger activators, a phorbol ester (12-O-tetradecanoylphorbol-13-acetate) and forskolin, in the regulation of GnRH-R gene expression in the alpha T3-1 gonadotrope cell line. Using Northern blot analysis to monitor endogenous GnRH-R steady state messenger RNA (mRNA) levels, we found that although GnRH and 12-O-tetradecanoylphorbol-13-acetate do not change GnRH-R mRNA levels, forskolin causes a time-dependent decline. All three treatments stimulate glycoprotein alpha-subunit gene expression. To dissect the molecular mechanism of forskolin action on GnRH-R gene expression, de novo RNA synthesis was inhibited with the transcription inhibitor, actinomycin-D (act-D). Act-D alone does not change GnRH-R message levels. However, in the presence of both act-D and forskolin, GnRH-R mRNA levels decline dramatically. These data demonstrate that forskolin alters GnRH-R posttranscriptionally by destabilizing its mRNA. Our data do not, however, exclude possible direct transcriptional effects. This study suggests that activators of the protein kinase-A pathway may alter gonadotrope sensitivity to GnRH by decreasing GnRH-R gene expression and, therefore, indirectly affect reproductive status.
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PMID:Down-regulation of the gonadotropin-releasing hormone receptor messenger ribonucleic acid by activation of adenylyl cyclase in alpha T3-1 pituitary gonadotrope cells. 789 46

Treatment of F344 rats with diethylstilbestrol (DES) for 1-2 months induces a prolactin (PRL)-secreting pituitary adenoma. After 8 weeks of DES treatment, we have shown that the ratio of regulatory subunits of the cAMP-dependent protein kinase (RI/RII) increased in the tumors. Presently we report the variations in RI/RII ratio, pituitary weight, DNA content, serum PRL, nuclear estrogen receptor (E2R) and of ornithine decarboxylase (ODC) activity from the time of DES pellet implantation until 8 weeks. Pituitary weight, DNA content and serum PRL rose significantly at 4 weeks with a maximum at 6-8 weeks, and significantly correlated with each other. E2R and ODC activity increased from week 1 onwards, with a maximum at 2 weeks and decreased at 8 weeks. Both variables showed a positive correlation but neither E2R nor ODC activity correlated with pituitary weight, DNA or serum PRL. Values for RI remained stable with time, but RII decreased progressively. The RI/RII ratio was maintained around unity between 1-4 weeks, increasing to 1.6-2 thereafter. This ratio positively correlated with pituitary weight and DNA. It is suggested that during tumor induction by estrogen in a sensitive strain of rats, growth signals with different time-courses become activated. Increases in pituitary weight and DNA content, indicators of mammotroph hypertrophy and hyperplasia, were preceded by early rises in E2R and ODC activity. Increases in the RI/RII ratio accompanied the adenomatous change, suggesting their role in cell transformation after 6 weeks of estrogen exposure.
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PMID:Biochemical parameters in the anterior pituitary during the course of tumorigenesis induced by diethylstilbestrol treatment. 798 Nov 27


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