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)

Tissue-type plasminogen activator (tPA) secretion is a specific response of Sertoli cells to follicle-stimulating hormone (FSH), which is lower after preincubation of the cells with low FSH concentrations because of FSH receptor/Gs protein uncoupling. In this report, we present evidence that this desensitization induced by the lowest FSH concentrations is suppressed by specific peptidic inhibitors of endogenous PKA and PKC in permeabilized Sertoli cells. In contrast, desensitization promoted by slightly higher FSH concentrations is not mediated through PKA or PKC activation but is dependent on protein neosynthesis.
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PMID:Protein kinases and protein synthesis are involved in desensitization of the plasminogen activator response of rat Sertoli cells by follicle-stimulating hormone. 792 33

This study was conducted to investigate whether endothelin-1 (ET-1) has direct effects on the functions of porcine granulosa cells harvested from small or medium follicles. Positive ET-1-like immunoreactivity (ET-1-LI) was observed in the cultured porcine granulosa cells, and Northern blot analysis demonstrated the expression of mRNA for prepro-ET-1 in these cells. The binding study showed the presence of a nonselective, single class of binding sites which predominantly included the subtype ETB. Increased ET-1-LI was detected in human follicular fluid obtained from the patients with stimulated ovarian cycles. ET-1 stimulated basal and follicle-stimulating hormone (FSH)-stimulated secretion of progesterone during short-term incubation (2 h), while it inhibited FSH- and human-chorionic-gonadotropin-stimulated accumulation of progesterone during long-term incubation (48 h) of immature or moderately mature granulosa cells. ET-1 significantly increased DNA synthesis in the cells. These biological actions were induced by ET-1, probably via a cAMP-protein kinase A pathway and intracellular calcium mobilization-protein kinase C pathway. The results suggest that ET-1 exerts autocrine/paracrine effects on porcine granulosa cell functions.
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PMID:Endothelin-1 as a local ovarian regulator in porcine granulosa cells. 808 93

In this study the localization and regulation of steady-state follistatin messenger ribonucleic acid (mRNA) levels in testicular cell cultures were examined with a solution-hybridization assay using a specific 32P-labelled cytosolic RNA antisense probe for follistatin and a 35S-labelled cytosolic RNA antisense probe for cyclophilin as internal standard. Testes from immature rats were dispersed with collagenase and fractionated in Sertoli and Leydig cell-enriched cultures. Follistatin mRNA was mainly localized to the Sertoli cell-enriched fraction and the expression of follistatin mRNA could be stimulated in vitro with fetal calf serum, epidermal growth factor or phorbol-12-myristate-13-acetate (an activator of protein kinase C), whereas follicle-stimulating hormone and forskolin (an activator of protein kinase A) had no effect. Neither prostaglandin E2, the synthetic glucocorticoid RU 28362 or all-trans-retinoic acid, which all regulate follistatin mRNA levels in non-testicular cell types, nor extracellular adenosine triphosphate (a purinergic receptor agonist) or testosterone had any obvious influence on follistatin mRNA levels in Sertoli cell-enriched cultures. From this study it is concluded that Sertoli cells are likely to be the source of follistatin expression in the rat testis, that follistatin mRNA levels in Sertoli cell-enriched cultures are subjected to regulation by epidermal growth factor and the protein kinase C-dependent pathway but are not regulated by extracellular adenosine triphosphate, follicle-stimulating hormone, all-trans-retinoic acid, prostaglandin E2, forskolin, testosterone or the glucocorticoid RU 28362 and that the regulation of follistatin mRNA is sex- and tissue-specific.
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PMID:Expression of follistatin messenger ribonucleic acid in Sertoli cell-enriched cultures: regulation by epidermal growth factor and protein kinase C-dependent pathway but not by follicle-stimulating hormone and protein kinase A-dependent pathway. 810 86

It has been well established that the biochemical and morphological changes during maturation of granulosa cells that are induced by follicle-stimulating hormone (FSH) occur through the elevation of intracellular cAMP and consequent activation of the cAMP-dependent protein kinase (PKA). In this report we show that FSH action alters the expression of A-Kinase Anchoring Proteins (AKAPs), which function to target the subcellular distribution of the type II PKA. Exposure of granulosa cells grown in primary culture with FSH and estradiol for 72 h resulted in the up-regulation of an 80-kDa AKAP and the RII beta subunit of PKA, whereas cells grown in control medium containing only estradiol produced a time-dependent increase of a 140-kDa AKAP. RII overlays performed with [32P]RII alpha preferentially detected RII-binding bands of 80 and 95 kDa compared to blots probed with [32P]RII beta, suggesting that FSH may alter the subcellular location of PKA in an isoform-specific manner. FSH treatment causes a translocation of RII alpha from the particulate to the cytosolic fraction coincident with the induction of the 80-kDa AKAP, which is also predominately cytosolic. These data suggest that FSH promotes a redistribution of the type II PKA holoenzyme through the selective induction of an RII isoform-specific AKAP.
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PMID:Follicle-stimulating hormone regulation of A-kinase anchoring proteins in granulosa cells. 840 95

Aromatase (CYP19) mRNA is induced by follicle-stimulating hormone (FSH) in granulosa cells of preovulatory follicles and subsequently is rapidly diminished as a consequence of the luteinizing hormone (LH) surge. Primary cultures of rat granulosa cells were used to identify some of the cellular mechanisms by which FSH increases and LH decreases steady-state levels of aromatase mRNA. Induction of aromatase mRNA by FSH was increased by cycloheximide but was blocked by alpha-amanitin and the C-kinase activators gonadotropin-releasing hormone (GnRH) and phorbol 12-myristate 13-acetate (PMA). In contrast, the decrease in steady-state levels of aromatase mRNA by LH was mimicked by A-kinase (forskolin) and C-kinase (PMA or GnRH) activators. The decrease in aromatase mRNA was associated with decreased amounts of mRNA and protein for steroidogenic factor-1 (SF-1), a nuclear orphan receptor that binds and trans-activates the aromatase promoter, and with the A-kinase subunit type II (RII beta), which is required for mediating cAMP action in these cells. The down-regulation of aromatase, SF-1, and RII beta by each kinase activator and alpha-amanitin was prevented by cycloheximide when the drug was added in combination with the activator. If, however, cycloheximide was added 2 h after PMA (or LH), the drug did not prevent the rapid loss of mRNA. When granulosa cells were transfected with an aromatase CAT transgene, CAT activity was stimulated 10- to 20-fold by FSH and forskolin but not by PMA. Taken together, these results indicate that the A-kinase but not the C-kinase pathway can trans-activate the aromatase gene in immature granulosa cells, whereas the C-kinase, as well as A-kinase pathways, mimic the LH surge to decrease aromatase mRNA in preovulatory cells. By increasing degradation of aromatase mRNA and by inhibiting transcription, the LH surge rapidly terminates the granulosa cell pattern of gene expression while reprogramming the cells to express genes associated with ovulation and luteinization.
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PMID:Expression of aromatase in the ovary: down-regulation of mRNA by the ovulatory luteinizing hormone surge. 902 37

We have previously demonstrated that there exist two distinct genes for the thermostable inhibitor protein of the cAMP-dependent protein kinase, PKIalpha and PKIbeta (Van Patten, S. M., Howard, P., Walsh, D. A., and Maurer, R. A. (1992) Mol. Endocrinol. 6, 2114-2122). We have also shown that in the testis, at least eight forms of PKIbeta exist, differing as a result of at least post-translational modification and alternate translational initiation (Kumar, P., Van Patten, S. M., and Walsh, D. A. (1997) J. Biol. Chem. 272, 20011-20020). We now report that in the testis, there is a unique cellular distribution of protein kinase inhibitor forms, with PKIbeta being essentially (if not exclusively) a germ cell protein and PKIalpha being expressed primarily in Sertoli cells. Furthermore, there is a progressive change in the forms of PKIbeta that are present within germ cells with development that is initiated in testis tubules and continues as the germ cells migrate through the epididymis. These conclusions are derived from studies with isolated cell populations and with the at/at germ cell-deficient mouse line, by in situ hybridization, and by following the developmental expression of these proteins in both testis and epididymis. We have also shown that follicle-stimulating hormone (FSH) can increase the expression of both PKIalpha and PKIbeta. The FSH-regulated expression of PKIalpha in the Sertoli cell likely occurs via the normal route of second messenger signal transduction. In contrast, the FSH-dependent PKIbeta expression must arise by some form of Sertoli cell-germ cell intercommunication.
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PMID:Specific testicular cellular localization and hormonal regulation of the PKIalpha and PKIbeta isoforms of the inhibitor protein of the cAMP-dependent protein kinase. 924 72

This study was designed to investigate the effect of follicle-stimulating hormone (FSH) on nuclear maturation, fertilization, and early embryonic development of in-vitro-matured bovine oocytes and to find out whether this effect is exerted through a cyclic adenosine monophosphate (cAMP) signal transduction pathway. In addition the effect of the combination of FSH and growth hormone (GH) on subsequent cleavage and embryo development was studied. Therefore cumulus oocyte complexes were cultured in the presence of FSH (0.05 IU/ml) and the nuclear stage of the oocytes was assessed using 4,6-diamino-2-phenyl-indole (DAPI) staining either after 16, 20, or 24 hr of in vitro maturation or 18 hr after the onset of fertilization. To assess the effect of FSH and the combination of FSH and GH added during in vitro maturation on the developmental capacity of the oocytes, cumulus oocyte complexes were incubated in the presence of either FSH (0.05 IU/ml) or FSH (0.05 IU/ml) plus GH (100 ng/ml) for 22 hr, followed by in vitro fertilization and in vitro embryo culture. To investigate whether FSH-induced oocyte maturation is exerted through the cAMP pathway, cumulus oocyte complexes were cultured in M199 supplemented with FSH (0.05 IU/ml) and H-89 (10 microM), a specific inhibitor of cAMP-dependent protein kinase A. After 16 hr of culture, the proportion of oocytes in metaphase II (MII) stage was determined. Cultures with GH and without FSH and H-89 served as controls. The percentage of MII oocytes at 16 hr of incubation was significantly lower (P < 0.001) in the presence of FSH than in the control group, while the number of MII oocytes beyond 20 hr did not differ from the control group. That points to a transient inhibition of nuclear maturation by FSH. Opposite to FSH, addition of GH during in vitro maturation significantly enhanced the number of MII oocytes after 16 hr of culture (P < 0.001), which points to the acceleration of nuclear maturation by GH. Addition of FSH during in vitro maturation significantly enhanced the proportion of normal fertilized oocytes, cleaved embryos and blastocysts (P < 0.001). Similarly, addition of GH during in vitro maturation significantly enhanced the number of cleaved embryos and blastocysts (P < 0.001); however, in vitro maturation in the presence of GH and FSH did not result in an extra enhancement of the embryo development. Both the inhibition of nuclear maturation by FSH and its acceleration by GH was completely abolished by H-89. In conclusion, in vitro maturation of bovine oocytes in the presence of FSH retards nuclear maturation via a cAMP-mediated pathway, while it enhances fertilizability and developmental ability of the oocytes. Supplementation of GH and FSH during in vitro maturation did not result in an extra increase in the number of blastocysts following in vitro fertilization and in vitro embryo culture.
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PMID:Follicle-stimulating hormone and growth hormone act differently on nuclear maturation while both enhance developmental competence of in vitro matured bovine oocytes. 977 55

Activins were originally isolated based on their ability to stimulate follicle-stimulating hormone secretion but later they have been shown to regulate a number of different cellular functions such as nerve cell survival, mesoderm induction during early embryogenesis as well as hematopoiesis. We studied the regulation of activin A, a homodimer of betaA-subunits, mRNA and protein in K562 erythroleukemia cells, which are known to be induced toward the erythroid lineage in response to activin or TGF-beta or toward the megakaryocytic lineage by the phorbol ester protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). Here we show by Northern blot analysis as well as by Western and ligand blotting that TPA strongly promotes activin betaA-subunit mRNA and activin A protein expression in K562 cells in time- and concentration dependent manner. In contrast, neither activin A nor TGF-beta induced betaA-subunit mRNA expression during erythroid differentiation in K562 cells. Interestingly, whereas activin type II receptors are not regulated during K562 cell differentiation (Hilden et al. (1994) Blood 83, 2163-2170), we now show that the activin type I and IB receptor mRNAs are clearly induced by TPA but not by activin or TGF-beta. We also show that the inducing effect of TPA on expression of activin betaA-subunit mRNA is potentiated by the protein kinase A activator 8-bromo-cAMP. We conclude that activin A and its type I receptors appear to be co-ordinately up-regulated during megakaryocytic differentiation of K562 cells.
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PMID:Co-ordinate expression of activin A and its type I receptor mRNAs during phorbol ester-induced differentiation of human K562 erythroleukemia cells. 1045 61

The regulation of retinoic acid receptor alpha (RARalpha) signal transduction has not been well characterized. In this study, we determined whether all-trans-retinoic acid (tRA) and follicle-stimulating hormone (FSH) modulate RARalpha receptor subcellular localization, leading to changes in its transcriptional activity and protein expression in mouse Sertoli cell lines. We found that tRA induced the nuclear localization of RARalpha within 30 min and that longer term exposure increased the receptor transcriptional activity and RARalpha protein expression. Conversely, FSH suppressed the tRA-induced nuclear localization, transcriptional transactivation, and protein expression of RARalpha. Treatment with two different protein kinase A-selective antagonists reversed the inhibitory actions of FSH on tRA-dependent RARalpha nuclear localization and transcriptional activity. These results are consistent with the involvement of protein kinase A in mediating the inhibitory effects of FSH. For the first time, we demonstrate a unique signaling convergence between the RARalpha and the FSH-mediated signaling pathways, which may have significant implications in the testis because both are critical regulators of testis physiology.
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PMID:Follicle-stimulating hormone inhibits all-trans-retinoic acid-induced retinoic acid receptor alpha nuclear localization and transcriptional activation in mouse Sertoli cell lines. 1066 May 75

The present study was performed to determine when follicle-stimulating hormone (FSH) begins to promote Sertoli cell division in fetal rats, and to determine whether the effect of FSH is mediated by cAMP-dependent protein kinase (PKA). When testes from 15- to 17-day fetuses were cultured with or without FSH for 48 h, FSH did not promote Sertoli cell division in 15-day testes, but did in 16- and 17-day testes. Anti-rat FSH was injected into 16-day fetuses in utero. Twenty-four hours later, the testes of the injected fetuses and those of their intact littermates were cultured with or without FSH for 48 h. Without FSH, the Sertoli cell division index was significantly lower in anti-FSH-treated fetuses than in intact fetuses. With FSH, however, the index increased. When PKA inhibitor was added to cultures of 16-day testes with FSH, the promotion of Sertoli cell division by FSH was inhibited. We conclude that between 16 and 17 days of gestation, fetal pituitary FSH stimulates the division of Sertoli cells by activating the PKA activity.
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PMID:Effect of follicle-stimulating hormone on sertoli cell division in cultures of fetal rat testes. 1087 22


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