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)

The ontogeny of ovarian cyclic AMP-binding and protein kinase activities during the postnatal development of the rat, as well as the effect of LH and FSH administration on ovarian cyclic AMP-binding and protein kinase activities in 5-day-old and in hypophysectomized rats was examined. Ovaries of 4 to 8-day-old rats possessed little or no measureable cyclic AMP-binding and protein kinase activities. Subsequent postnatal development occurred in three distinct phases. During the first phase, ovarian cyclic AMP-binding and protein kinase activities increased progressively from age 8 days to age 23 days, when adult levels were observed. Protein kinase activity declined markedly during the second postnatal developmental phase from days 24 to 26, lost its cyclic AMP-dependency, and became refractory to stimulation by cyclic AMP. Studies employing a heat-stable protein kinase inhibitor protein isolated from rabbit skeletal muscle suggest that ovarian protein kinase activity during the refractory period was largely of the cyclic AMP-independent variety. During the third postnatal phase, comprising days 30 to 40, ovarian cyclic AMP-binding and protein kinase activities increased to levels seen in sexually mature rats. Protein kinase cyclic AMP-dependency which was lost during the refractory second postnatal period was fully restored during the third phase. Administration of FSH or LH led to a marked increase of ovarian cyclic AMP-binding and protein kinase activities in 5-day-old rats. Hypophysectomy of 20-day-old rats caused a significant reduction of the cyclic AMP-binding and protein kinase activities in a 27,000 X g supernatant fraction, as well as in the mitochondrial, microsomal, and 105,000 X g supernatant fraction. The decreased cyclic AMP-binding and protein kinase activities of these fractions could be partially restored by FSH or LH treatment of the hypophysectomized rats. The results indicate that ovarian cyclic AMP-binding and protein kinase activities, as well as the ability of ovarian protein kinase to respond to cyclic AMP are gradually acquired after the first postnatal week. The postnatal development of ovarian protein kinase and cyclic AMP-binding activities presumably involves the participation of FSH and LH, although the precise mechanism of LH and FSH action remains to be established.
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PMID:Ovarian cyclic adenosine monophosphate-dependent protein kinase activity: ontogeny and effect of gonadotropins. 17 26

The Sertoli cell of the rat testis contains two cytoplasmic forms of adenosine 3',5' monophosphate (cyclic AMP)-dependent protein kinase, designated as Peak I and Peak II, which change in relative proportion during Sertoli cell maturation. Peak I and Peak II differ in their subunit interaction. Thus, while the substrates, ATP and histone, affect cyclic AMP binding to Peak I, neither of these compounds affect the binding of cyclic AMP to the Peak II enzyme. The effects of cyclic AMP binding to Peak I appear to be due to the fact that histone and high ionic strength cause dissociation of the Peak I holoenzyme, whereas ATP stabilizes the holoenzyme complex against dissociation. The Peak II holoenzyme is not affected by either salt of histone and is only dissociated by cyclic AMP. Once dissociated, the subunits of Peak II will rapidly reassociate under low salt conditions whereas the subunits of Peak I will not reassociate. By utilizing the distinct properties of Peak I and Peak II, it is possible to demonstrate the activation of both Peak I and Peak II Sertoli cell protein kinase in response to FSH.
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PMID:Characterization and follicle stimulating hormone activation of Sertoli cell cyclic AMP-dependent protein kinases. 19 15

Cytosol of mature estrous rabbit follicles contains a single species of protein kinase, protein kinase 3, which can be classified as a type II cAMP-dependent protein kinase. Cytosol of functional rabbit corpora lutea (CL) contains, in addition to protein kinase 3, a second species of kinase activity, protein kinase 2, which can be classified as a type I cAMP-dependent protein kinase. These conclusions are based upon the relative dissociation and reassociation characteristics of the two holoenzymes in the presence and absence of 0.5 M NaCl after in vitro dissociation by cAMP, upon the effect of MgATP on salt- and basic protein-induced dissociation, and upon their relative elution from DEAE-cellulose. Protein kinase 3 in mature estrous rabbit follicles was rapidly activated after an iv injection of hCG. The activation was demonstrated by an increase of the protein kinase activity ratio as well as by the appearance of the free catalytic subunit of protein kinase upon Sephadex gel filtration. Maximal activation occurred within 10 min of in vivo hormone administration and required ovulatory doses of hormones with LH-like activity. Neither PRL, ACTH, epinephrine, nor a highly purified preparation of FSH promoted activation of the follicular protein kinase 3. Demonstration of protein kinase activation in follicles was achieved in the presence of 0.5 M NaCl in the homogenization media. After an iv injection of hCG, a partial activation of luteal protein kinases 2 and 3 was demonstrated, as reflected by the increase of the protein kinase activity ratio. These results implicate an important role for cAMP-dependent protein kinase 3 in LH action in rabbit ovarian follicles and for cAMP-dependent protein kinases 2 and 3 in LH action in rabbit CL.
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PMID:Rabbit ovarian protein kinases. III. Gonadotrophin-induced activation of soluble adenosine 3',5'-monophosphate-dependent protein kinases. 21 48

Studies on the gonadotrophin-responsive adenylyl cyclase (AC) system of rabbit and porcine ovarian follicles reveal that hCG or LH-induced desensitization of the AC system can be divided into two phases: an initial, LH-specific phase and a second phase which is not specific for LH. The first phase occurs within the first hour after LH-hCG-receptor interaction, is agonist specific, and is not mediated by protein synthetic events or by cAMP. In view of our previous demonstration of the critical dependence of the LH-induced desensitizing process in cell-free membrane preparations of porcine follicles upon Mg2+ and ATP, we investigated the role of a phosphorylation reaction in the first phase of the AC desensitizing process. Porcine follicular membranes rich in LH-sensitive AC activity were found to contain the molecular requirements necessary for a phosphorylation reaction: namely, cAMP-dependent and cAMP-independent protein kinases as well as phosphoprotein phosphatases. The following lines of indirect evidence indicated that reversal or resensitization of the desenzitized AC system to LH was mediated by a dephosphorylation reaction. Activators of endogenous phosphoprotein phosphatases--Mn2+ and dithiothreitol--promoted a specific resensitization of the follicular AC system to LH. Likewise, a partially purified phosphoprotein phosphatase also resensitized the desensitized, LH unresponsive AC to LH, and boiling of the phosphatase prevented its effect. LH-induced desensitization of the AC system, on the other hand, did not appear to be mediated by a cAMP-dependent protein kinase, as evidenced both by the inability of beef heart protein to promote desensitization of AC and by the inability of an inhibitor of cAMP-dependent protein kinase to prevent LH-induced densensitization. The second phase of desensitization, which occurs after the first hour following hCG-LH-receptor interaction, is characterized by a loss of responsiveness to FSH as well as to LH and can be promoted by dibutryl cAMP (in the absence of LH). These results provide new evidence on the characteristics and molecular mechanism of LH-induced densensitization of the follicular AC system. These results indicate that the level of phosphorylation of membrane-associated components may, in part, regulate the activity of the AC system during this first phase of homologous desensitization.
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PMID:LH-induced desensitization of the adenylyl cyclase system in ovarian follicles. 22 90

Two distinct isoforms of prostaglandin (PG) endoperoxide synthase (PGS) have been identified in rat ovarian tissues: rPGSi (mol wt, 70,000-72,000) is induced by FSH and LH in preovulatory follicles, whereas the other isoform (mol wt, 69,000) is not. Induction of rPGSi is associated with LH-stimulated increases in PG biosynthesis obligatory for ovulation. Because GnRH, like LH, can also stimulate the synthesis of PGs and ovulation in the rat, this study was undertaken to determine which isoform of PGS might be induced by GnRH, in what cell type, and by what intracellular pathways. Results show that GnRH at relatively low concentrations (10(-8)-10(-7) M) induced the same isoform of PGS (rPGSi) in the same cell type (preovulatory granulosa cells) and within the same 5- to 7-h time course as did LH. Unlike LH and FSH, GnRH did not cause a major increase in cAMP, nor did GnRH induce luteinization. The effects of GnRH on rPGSi in preovulatory follicles were not mimicked by known activators of protein kinase-C (phorbol myristate acetate, bryostatin, diacyglycerol, and (+/-)ionomycin). Epidermal growth factor (but not basic fibroblast growth factor or platelet-derived growth factor), which activates a receptor-associated tyrosine kinase, caused a small increase in rPGSi. Genistein, a selective inhibitor of tyrosine kinases, blocked GnRH and LH induction of rPGSi. Taken together these results suggest that the mechanisms by which GnRH and LH selectively induce rPGSi in granulosa cells of preovulatory follicles before ovulation may converge at some step within a cellular tyrosine kinase cascade. Furthermore, the mechanisms responsible for inducing rPGSi are distinct from those required for cellular luteinization.
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PMID:Induction of prostaglandin H synthase in rat preovulatory follicles by gonadotropin-releasing hormone. 131 86

To study the mechanism of inhibin action on the release of FSH, the effect of porcine follicular fluid (pFF) on the LH-RH binding to the anterior pituitary cells as well as cyclic AMP (cAMP) and diacylglycerol (DAG) content in the pituitary cells were examined in monolayer cultures of the rat anterior pituitary cells. The suppression of the binding of labeled LH-RH to the pituitary cells was not affected by pFF. Neither the LH-RH receptor concentration nor the affinity of LH-RH with the binding sites was affected by pFF according to the Scatchard analysis. A dose-related decrease in FSH content in the conditioned media was observed in the pFF-treated culture wells, whereas luteinizing hormone levels remained unaltered by pFF. There was no significant difference between pFF-treated and untreated groups in cAMP or DAG content in the rat anterior pituitary cells. These data may indicate that inhibin has no effect on the LH-RH receptor, suggesting the presence of its own receptor on the gonadotropes. Messenger system(s) other than A-kinase and C-kinase systems in the cells may be involved in the suppression of FSH by inhibin.
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PMID:[Studies on the suppression mechanism of follicle-stimulating hormone (FSH) release by porcine follicular fluid]. 132 32

Changes in cAMP-dependent phosphorylation of 53 kDa protein in a human ovary with respect to the aging process were studied. The phosphorylation of endogenous proteins in ovarian cytosol decreased with aging. However, ovarian aging was accompanied by an increase in the cAMP-dependent phosphorylation of 53 kDa specific protein while the amount of this protein decreased with aging. The plasma gonadotropin levels of women with regular menstrual periods were significantly different from those of women whose menstrual periods had in the recent past become irregular (FSH: p less than 0.01; LH: p less than 0.05); however, there was no significant difference in the plasma estradiol levels between these two groups. Our data show the possible correlations between the non-steroidal ovarian factor (53 kDa protein) and/or its phosphorylation by cAMP-dependent protein kinase and the ovarian aging process.
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PMID:Changes in cAMP-dependent phosphorylation of specific cytosol protein in the peri- and postmenopausal ovary. 132 60

We have investigated the regulatory actions of endothelin-1 (ET-1) on inositol phosphate accumulation, cytosolic free Ca2+ ion concentrations ([Ca2+]i), and basal and FSH-stimulated progesterone and cAMP accumulation by swine granulosa cells in serum-free cultures. ET-1 induced a rapid stimulation of phosphoinositide hydrolysis in populations of granulosa cells, as inferred by the rapid appearance of soluble inositol polyphosphates in response to ET-1 exposure. At the single cell level, fura-2 videomicroscopy was used to measure [Ca2+]i in individual granulosa cells. We observed cell-cell variability in the threshold concentration of ET-1 required to induce a rise in [Ca2+]i. More than 75% of granulosa cells responded to maximal doses of ET-1. The following parameters of [Ca2+]i were influenced by ET-1 concentration: percentage of responding cells, lag time for the onset of response, amplitude, and kinetics of the response. Two types of ET-1-mediated [Ca2+]i rises were observed. One type exhibited rapid Ca2+ kinetics, reaching at least a 2-fold increase above basal (spike phase) within 1-10 sec and returning to a new steady state (plateau phase) 2 min after onset. The other mode of response had slower [Ca2+]i kinetics, in which 50 sec or more were required to double [Ca2+]i, which remained at this level throughout the observation period (2.5 min). These responses to ET-1 were specific and were not initiated by vasopressin or tumor necrosis factor-alpha. In cell population studies using monolayer cultures of swine granulosa cells, ET-1 inhibited FSH-stimulated accumulation of progesterone and cAMP. The ET-1-mediated inhibition of FSH-stimulated accumulation of progesterone required at least 4 h of ET-1 exposure. The ET-1-mediated inhibition of both the FSH-stimulated accumulation of progesterone and cAMP after 24-h incubation was mimicked by an activator of protein kinase-C, phorbol 12-myristate 13-acetate, but not by an inactive phorbol. These observations in either single cells or populations of swine ovarian (granulosa) cells are consistent with a possible regulatory role of an ET-1-activated intracellular signaling pathway involving inositol phosphates, [Ca2+]i, and protein kinase-C in the mammalian granulosa cell.
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PMID:Actions of endothelin-1 on swine ovarian (granulosa) cells. 132 59

We have previously shown that basic fibroblast growth factor (bFGF) inhibits the FSH-induced differentiation of cultured rat granulosa cells, as manifested by prominent reduction of the LH receptor expression. We now investigate the possible sites and mechanism of action of bFGF. Whereas bFGF decreased the cAMP formation induced by FSH, it enhanced the cAMP production caused by cholera toxin and forskolin, suggesting that bFGF exerted its inhibitory action on cell differentiation at a step to cAMP production. Photoaffinity labeling with 8-azido-[32P]cAMP revealed that bFGF markedly reduced the FSH-induced increase in the level of regulatory subunit RII beta of the cAMP-dependent protein kinase (PKA) type II. In contrast to its striking effect on RII beta expression (70-80% inhibition), bFGF decreased PKA enzymatic activity by only 30%. On the other hand, transforming growth factor-beta (TGF beta) slightly amplified the stimulatory action of FSH and antagonized the bFGF inhibitory effect on both LH receptor expression and RII beta synthesis. We report that the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA), which impaired granulosa cell differentiation, also abolished the RII beta synthesis induced by FSH. The activation of PKC by bFGF in granulosa cells was supported by the following findings: (i) bFGF markedly enhanced the production of diacylglycerol (2.3-fold stimulation at 5 min), the intracellular activator of PKC; (ii) bFGF promoted tight association of PKC to cellular membranes, a process that is believed to correlate with the enzyme activation; (iii) bFGF induced the phosphorylation of an endogenous M(r) 78,000/pI 4.7 protein that appears as a specific PKC substrate; (iv) bFGF mimicked the TPA-induced transmodulation of the epidermal growth factor (EGF) receptor, reducing by 36% the 125I-EGF binding on granulosa cells. We conclude that bFGF may exert its repressive action on RII beta synthesis, PKA activity, and granulosa cell differentiation by primarily targeting PKC activation.
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PMID:Regulation of cyclic adenosine 3',5'-monophosphate-dependent protein kinase activity and regulatory subunit RII beta content by basic fibroblast growth factor (bFGF) during granulosa cell differentiation: possible implication of protein kinase C in bFGF action. 132 4

We have previously demonstrated FSH-induced increases in cytosolic free calcium ion concentrations ([Ca2+]i) in single granulosa cells. We report here on the role of cAMP-dependent protein kinase (PKA) in the FSH-induced [Ca2+]i increase using swine granulosa cells. The R-isomer of cAMP (Rp-cAMPS) and a synthetic peptide containing the active core region of the PKA inhibitor were used as specific inhibitors of PKA. The Rp-cAMPS dose used was effective in completely abolishing FSH-stimulated progesterone production by cultured granulosa cells. However, FSH retained its ability to initiate a calcium signal even in the presence of the cAMP antagonist. In addition, both Rp-cAMPS and the PKA inhibitor peptide significantly reduced the percentage of granulosa cells able to generate [Ca2+]i signals in response to 8-bromo-cAMP without affecting the percentage of [Ca2+]i responses to FSH. We conclude from these observations that at least two aspects, percentage of responding cells and kinetics of the response, of FSH-induced [Ca2+]i increases in swine granulosa cells appear to be independent of the action of PKA. Such findings suggest a direct action of cAMP on [Ca2+]i or cAMP-independent action(s) of FSH in granulosa cells.
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PMID:Is the calcium signal induced by follicle-stimulating hormone in swine granulosa cells mediated by adenosine cyclic 3',5'-monophosphate-dependent protein kinase? 154 16


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