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)

Stimulation of cultured hypothalamic slices with PRL causes a rapid translocation of a Ca2+/phospholipid dependent protein kinase from the cytosol to the membrane fraction. The translocation of PKC from the cytosol to the membrane occurred at physiological concentrations of PRL with a maximal response occurring at 10(-10) M. At concentrations above this, there was less PKC activity translocated from the cytosol to the membrane. When injected into the medial preoptic area of the hypothalamus, PRL resulted in a similar translocation of PKC activity. These data clearly indicate that PRL can activate PKC in the rat hypothalamus, and suggest that PKC may be one of the transmembrane signaling mechanisms involved in the regulation of brain function by prolactin.
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PMID:Prolactin stimulation of protein kinase C activity in the rat hypothalamus. 202 80

The relationship between 5-hydroxyeicosatetraenoic acid (5-HETE) and calcium-activated, phospholipid-dependent protein kinase (protein kinase C) in prolactin (PRL) release was investigated in rat anterior pituitary cells. Arachidonic acid or 5-HETE, a 5-lipoxygenase metabolite of arachidonic acid, is known to cause a significant concentration-dependent increase in PRL release. Phorbol 12-myristate 13-acetate (PMA) and dioctanoyglycerol (diC8) have also been known to stimulate PRL release from pituitary cells, so we showed that these PRL releases were correlated with the activation of protein kinase C, that is, they induced dose-dependent translocation of protein kinase C from the cytosol to the membrane. Arachidonic acid, however, did not cause a significant change in the distribution of protein kinase C. We also showed that the PRL release induced by arachidonic acid and that induced by 5-HETE were additional to that by 100 nM PMA. Thus we suggested that the signals for the stimulation of PRL release sent by arachidonic acid and 5-HETE would be different from the signal sent through protein kinase C by PMA.
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PMID:5-Hydroxyeicosatetraenoic acid and phorbol ester stimulate prolactin release from rat anterior pituitary cells by different mechanisms. 212 2

The intermediary role and relative importance of cAMP in follicle-stimulating hormone (FSH) hormonal action were reinvestigated at the level of the rat granulosa cell employing Rp-cAMPS, a novel antagonistic analog of cAMP. This approach may not only provide for direct documentation of cAMP dependence, but may also, by inference, highlight the potential relative importance of other putative intracellular second messenger systems. Initial cell-free validation studies indicated that Rp-cAMPS is capable of effectively competing with cAMP for binding to and activation of the regulatory subunit of the granulosa cell A-kinase holoenzyme. Subsequent whole-cell studies employed cultured rat granulosa cells, the cAMP-phosphodiesterase activity of which was suppressed with ZK62711. Basal progesterone accumulation was relatively low, remaining unaffected by treatment with a maximally effective dose of Rp-cAMPS by itself (10(-3) M). Whereas treatment with FSH (30 ng/ml) resulted in a substantial increase in progesterone accumulation, concurrent treatment with increasing concentrations (10(-6)-10(-3) M) or Rp-cAMPS brought about dose-dependent decrements in the FSH effect with a median effective dose of 1.8 +/- (SE) 0.4 x 10(-5) M and a maximal, but incomplete inhibitory effect of 70 +/- (SE) 6%. Higher concentrations of FSH (greater than or equal to 100 ng/ml) progressively diminished, but did not abolish the Rp-cAMPS blockade. Removal of Rp-cAMPS resulted in progressive resumption of FSH responsiveness suggesting reversibility of action. Significantly, Rp-cAMPS proved highly effective in blocking the action of its agonistic diastereomer Sp-cAMPS. However, Rp-cAMPS was unable to block the action of the lactogenic receptor agonist prolactin, the second messenger of which remains uncertain. Taken together, these findings provide additional direct support to the notion that cAMP may be an intracellular second messenger of FSH. However, to the extent that Rp-cAMPS is incapable of complete neutralization of FSH action, our findings further suggest that cAMP may play a central, albeit non-exclusive role in FSH-supported granulosa cell differentiation and that other putative second messenger systems may also be at play.
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PMID:Blockade of granulosa cell differentiation by an antagonistic analog of adenosine 3',5'-cyclic monophosphate (cAMP): central but non-exclusive intermediary role of cAMP in follicle-stimulating hormone action. 217 13

The possibility that chicken growth hormone (cGH) can be phosphorylated has been examined. Both native and biosynthetic cGH were phosphorylated by cAMP-dependent protein kinase (and gamma -32P-ATP). The extent of phosphorylation was however less than that observed with ovine prolactin. Under the conditions employed, glycosylated cGH was not phosphorylated. Chicken anterior pituitary cells in primary culture were incubated in the presence of 32P-phosphate. Radioactive phosphate was incorporated in vitro into the fraction immunoprecipitable with antisera against cGH. Incorporation was increased with cell number and time of incubation. The presence of GH releasing factor (GRF) increased the release of 32P-phosphate labelled immunoprecipitable GH into the incubation media but not content of immunoprecipitable GH in the cells. The molecular weight of the phosphorylated immunoreactive cGH in the cells corresponded to cGH dimer.
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PMID:Phosphorylation of chicken growth hormone. 221 76

Highly purified growth hormone (GH) has been isolated from Atlantic salmon (Salmo salar) pituitaries by extraction with acid acetone, acidic precipitation, and reversed-phase high-performance liquid chromatography (HPLC). The yield was 2.5 mg/g wet tissue. The Atlantic salmon GH (sGH) emerged as a single symmetrical peak after HPLC on a reverse phase C18 column. SDS-gel electrophoresis revealed only one band with an estimated molecular weight of 23,000. Atlantic sGH showed a uniform molecular weight, but two-dimensional (2D) gel electrophoresis of the purified sGH revealed charge heterogeneity with pI's ranging from 6.5 to 8.2. Treatment of the purified sGH with alkaline phosphatase concentrated these different forms into a single more alkaline position (pI 8.2) indicating removal of acidic groups. These results were documented using both silver- and immunostaining of the 2D SDS gels. The purified sGH was phosphorylated in vitro by a calmodulin-dependent protein kinase. Phosphorylation of sGH may be a post-translational modification resulting in several molecular forms with variable acidity. Analysis of the amino acid composition of Atlantic sGH revealed homology with GHs isolated from other teleost species and the amino-terminal sequence showed only three different amino acids within the first 25 residues compared to GH isolated from chum salmon (Oncorhynchus keta) and coho salmon (Oncorhynchus kisutch) pituitaries. Atlantic sGH had a methionine as the amino-terminal residue. Antibodies against chum sGH cross-reacted with Atlantic sGH. Antibodies against either Atlantic or chinook (Oncorhynchus tschawytscha) salmon prolactin or human GH did not cross-react with Atlantic sGH. Atlantic sGH was shown to have a slight growth-promoting activity in the rat tibia assay.
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PMID:Purification and characterization of Atlantic salmon growth hormone and evidence for charge heterogeneity. 228 75

The experimental accessibility of monolayer culture has been used to study signal transduction mechanisms in primary CNS neurons and clonal pituitary cells. Here we review results on two signals representative of the emerging diversity of mechanisms discovered in all species studied thus far. One is mediated by micromolar concentrations of the amino acid GABA at postsynaptic membranes throughout the mammalian CNS and involves transient activation of Cl- ion channels whose distribution of conducting periods accounts for the millisecond time course of the signal. This signal serves to depress the probability that the target cell will trigger an action potential. The signal intensifies as the postsynaptic membrane is depolarized and can be modulated by clinically important drugs, primarily through changes in channel kinetics. The other signal involves nanomolar concentrations of the peptide TRH, which stimulates secretion of prolactin from clonal "GH3" pituitary cells. Intracellular recordings of GH3B6 cells show that TRH triggers a complex electrical response lasting several minutes. The response consists of Ca2+-activated K+ conductance followed by Ca2+-action potential activity. Whole-cell patch recordings, which rapidly dialyze the cell, can eliminate the TRH-induced changes in membrane excitability. Inclusion of aqueous lysates of the GH3B6 clone or the soluble second messenger factors inositol trisphosphate (IP3) or protein kinase (PKC) can restore various aspects of the change in membrane excitability. Thus, TRH alters ion conductance mechanisms through a second messenger cascade likely to involve IP3-mediated mobilization of Ca2+ from the endoplasmic reticulum and transient translocation of PKC from cytoplasm to plasma membrane. These synaptic and extrasynaptic signals reflect some of the diversity of transduction mechanisms involved in intercellular communication.
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PMID:Signal transduction mechanisms in cultured CNS neurons and clonal pituitary cells. 244 68

We report the isolating and sequencing of three cDNA clones encoding rat P-450scc, the nucleotide and protein sequences of which are highly homologous to those of bovine and human P-450scc, especially in the putative heme and steroid binding domains. We document that different molecular mechanisms regulate P-450scc in granulosa cells of preovulatory (PO) follicles prior to and after luteinization. Luteinizing hormone/human chorionic gonadotropin (LH/hCG) and cAMP are obligatory to induce P-450scc mRNA in PO granulosa cells in vivo and in vitro. Once P-450scc mRNA is induced as a consequence of the LH/hCG surge it is constitutively maintained by luteinized cells in vivo (0-4 days) and in vitro (0-9 days) in the absence of gonadotropins, is susceptible to modulation by prolactin and is no longer regulated by cAMP. Exposure to elevated concentrations of hCG in vivo for 5-7 h was required for PO granulosa cells to undergo a functional transition establishing the stable luteal cell phenotype. Transient exposure of PO + hCG (7 h) follicles in vitro to the RNA synthesis inhibitor actinomycin D (1 microgram/ml) or the protein synthesis inhibitor cycloheximide (10 micrograms/ml), for 1-5 h prior to culturing the granulosa cells failed to disrupt the induction of P-450scc mRNA, progesterone biosynthesis, and appearance of the luteal cell morphology. Inhibitors of protein kinase A (Rp-cAMPS; 1-500 microM and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H8); 1-200 microM) added directly to the luteinized cell cultures also failed to alter P-450scc mRNA in these cells, although the cells contain in vivo amounts of mRNA for RII beta, RI alpha, and C alpha, the primary subunits of protein kinase A found in the rat ovary. These data suggest that expression of the P-450scc gene in rat ovarian follicular cells is regulated in a sequential manner by cAMP-dependent and cAMP-independent mechanisms associated with granulosa cells and luteal cells, respectively.
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PMID:Cyclic AMP-dependent and -independent regulation of cholesterol side chain cleavage cytochrome P-450 (P-450scc) in rat ovarian granulosa cells and corpora lutea. cDNA and deduced amino acid sequence of rat P-450scc. 248 Sep 59

The possible role of the catalytic subunit of the cAMP-dependent protein kinase in mediating the regulation of prolactin gene transcription has been investigated through the use of a synthetic gene encoding the heat-stable inhibitor of the cAMP-dependent protein kinase. To assess the effects of protein kinase inhibitor expression on cAMP induction of prolactin gene transcription, a marker gene containing the rat prolactin promoter and adjacent 5'-flanking sequences linked to the bacterial chloramphenicol acetyltransferase gene was cotransfected with a protein kinase inhibitor-expression vector. The results demonstrate that the protein kinase inhibitor-expression vector reduced both basal and cAMP-stimulated expression of the cotransfected prolactin-chloramphenicol acetyltransferase gene. A mutant protein kinase inhibitor-expression vector, coding for an inactive inhibitor protein, did not inhibit basal or cAMP-stimulated prolactin gene transcription. Furthermore, the protein kinase inhibitor-expression vector did not inhibit zinc induction of the metallothionein promoter. Analysis of protein kinase activity in transfected cells demonstrated that the protein kinase inhibitor expression vector reduced cAMP-dependent protein kinase activity but did not reduce protein kinase C activity. Nuclease protection experiments confirmed that the effects of the inhibitor vector involved changes in correctly initiated transcripts produced from the prolactin promoter. Surprisingly, the protein kinase inhibitor-expression vector reduced the effects of several different agents including epidermal growth factor, thyrotropin-releasing hormone, phorbol esters, and estrogen on prolactin gene expression to the same extent as it altered cAMP effects.
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PMID:A protein kinase inhibitor gene reduces both basal and multihormone-stimulated prolactin gene transcription. 253 42

Whereas molecular cloning experiments have provided evidence for the presence of two closely related genes for the catalytic subunit of the cAMP-dependent protein kinase, the possible interchangeability of these isoforms in initiating biological processes has not been examined. To test the role of the two forms of the kinase in regulating transcription, expression vectors containing the coding sequence of either kinase have been cotransfected with a fusion gene containing the prolactin promoter coupled to an appropriate marker gene. The results demonstrate that expression vectors for both isoforms of the catalytic subunit are able to increase prolactin promotor activity in a dose-dependent manner. The effects can be observed by measuring either marker gene activity or RNA levels. Transfection of an expression vector encoding an inactive catalytic subunit did not stimulate prolactin promoter activity. The results provide additional evidence for the role of the catalytic subunit of the cAMP-dependent kinase in mediating regulation of specific gene transcription and demonstrate that both forms of the catalytic subunit are capable of participating in the regulation of transcription.
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PMID:Both isoforms of the cAMP-dependent protein kinase catalytic subunit can activate transcription of the prolactin gene. 254 Jan 66

Ca2+ is a major regulator of exocytosis in secretory cells, however, the biochemical mechanisms underlying regulation remain to be identified. To render the secretory apparatus accessible for biochemical studies, we have developed a cell permeabilization method (cell cracking) which utilizes mechanical shear. GH3 pituitary cells subjected to cracking were permeable to macromolecules but retained a normal cytoplasmic ultrastructure including secretory granules. Incubation of the permeable cells at 30-37 degrees C with 0.1-1.0 microM Ca2+ and millimolar MgATP resulted in the release of the secretory proteins, prolactin (PRL) and a proteoglycan, but not lysosomal enzymes. Extensively washed permeable cells were incapable of releasing PRL in response to Ca2+ and MgATP addition. However, addition of cytosol was found to restore Ca2+-activated, MgATP-dependent PRL release. The cytosolic factor responsible for activity was thermolabile and protease sensitive. The protein was partially purified, and its molecular mass was estimated to be equivalent to that of a globular protein of 200-350 kDa by molecular sieve chromatography. Inhibitors of calmodulin or protein kinase C (trifluroperazine, calmidazolium, H-7) failed to inhibit Ca2+-activated PRL release, and the required cytosolic protein could not be replaced by purified calmodulin, calmodulin-dependent protein kinase II, protein kinase C, or calpactin I. Further purification and characterization of the cytosolic protein should reveal the nature of biochemical events involved in regulated secretory exocytosis.
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PMID:A new method for cell permeabilization reveals a cytosolic protein requirement for Ca2+ -activated secretion in GH3 pituitary cells. 272 69


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