Cyclic GMP and cyclic GMP-dependent protein kinase play important roles in physiologic processes such as relaxation of
vascular smooth muscle and inhibition of platelet aggregation. Two main forms of cGK have been identified: a soluble
form designated type I and an intrinsic membrane-bound form designated type II.
NCBI Summary:
Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act as key mediators of the nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. This PRKG1 gene on human chromosome 10 encodes the soluble Ialpha and Ibeta isoforms of PRKG by alternative transcript splicing. A separate gene on human chromosome 4, PRKG2, encodes the membrane-bound PRKG isoform II. The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth muscle tone, preventing platelet aggregation, and modulating cell growth. This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. [provided by RefSeq, Sep 2011]
General function
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Cellular localization
Cytoplasmic
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Ovarian function
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Expression regulated by
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cGMP/PKG-I pathway-mediated GLUT1/4 regulation by NO (nitric oxide) in female rat granulosa cells. Tian Y et al. (2018) Nitric oxide (NO) is a multifunctional gaseous molecule that plays important roles in mammalian reproductive functions including follicular growth and development. Although our previous study showed that NO mediated 3,5,3'-triiodothyronine (T3) and follicle-stimulating hormone (FSH)-induced granulosa cell development via upregulation of GLUT1 (glucose transporter protein ) and GLUT4 in granulosa cells, little is known about the precise mechanisms regulating ovarian development via glucose. The objective of the present study was to determine the cellular and molecular mechanism by which NO regulates GLUT expression and glucose uptake in granulosa cells. Our results indicated that NO increased GLUT1/GLUT4 expression and translocation in cells, as well as glucose uptake. These changes were accompanied by upregulation of cGMP level and PKG-I protein content. The results of siRNA analysis showed that knockdown of PKG-I significantly attenuated gene expression, translocation and glucose uptake. Moreover, the PKG-I inhibitor also blocked the above processes. Furthermore, NO induced CREB phosphorylation, and CREB siRNA attenuated NO-induced GLUT expression, translocation, and glucose uptake in granulosa cells. These findings suggest that NO increases cellular glucose uptake via GLUT upregulation and translocation, which are mediated through the activation of the cGMP/PKG pathway. Meanwhile, the activated CREB is also involved in the regulation. These findings indicate that NO has an important influence on the glucose uptake of granulosa cells.//////////////////
Ovarian localization
Theca
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Orstavik S, et al 1997 reported the characterization of the human gene encoding the type I alpha and
type I beta cGMP-dependent protein kinase (PRKG1).
The type I cGMP-dependent protein kinase (cGK) has been shown to play a crucial
role in the relaxation of vascular smooth muscle by lowering the intracellular level of
calcium. Two isoforms of type I cGK have been described, type I alpha and type I
beta, differing only in their N-terminal parts. This report describes the cloning of the
gene PRKG1 encoding both human type I cGK isoforms. PRKG1 is a single-copy
gene consisting of 19 exons encompassing at least 220 kb. Several of the splice sites
previously observed in the Drosophila melanogaster DG2 gene have been conserved
in PRKG1, and these conserved splice sites correlated well with the boundaries
between several of the previously proposed functional domains of type I cGK. The
first two exons of the type I cGK gene were shown to encode the type I alpha- and
type I beta-specific parts of the cGK. Using 5'-rapid amplification of cDNA ends,
potential sites for transcription initiation were identified 5' upstream of both these
exons. Northern blot analyses demonstrated distinct patterns of expression of the
isoforms of type I alpha and I beta cGK in different human tissues, including the ovary.
Follicle stages
Antral
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Cyclic GMP dependent protein kinase II is induced by LH and PR dependent mechanisms in granulosa cells and cumulus oocyte complexes of ovulating follicles Sriraman V, et al .
Cyclic GMP dependent protein kinase II (Prkg2, cGK II) was identified as a potential target of the progesterone receptor (nr3c3) in the mouse ovary based on microarray analyses. To document this further, the expression patterns of cGK II and other components of the cGMP signaling pathway were analyzed during follicular development and ovulation using the PMSG-hCG-primed immature mice. Levels of cGK II mRNA were low in ovaries of immature mice, increased 4-fold in response to PMSG and 5-fold more within 12 h after hCG, the time of ovulation. In situ hybridization localized cGK II mRNA to granulosa cells and cumulus oocyte complexes of periovulatory follicles. In progesterone receptor null mice, cGK II mRNA was reduced significantly at 12 h after hCG in contrast to heterozygous littermates. In primary granulosa cell cultures cGK II mRNA was induced by PMA, enhanced by adenoviral expression of PR-A and blocked by RU486 and trilostane. PR-A in the absence of PMA was insufficient to induce cGK II. Expression of cGK I (Prkg1) was restricted to the residual tissue and not regulated by hormones. Guanylate cyclase-A (Npr1; GC-A)) mRNA expression increased 6-fold by 4 h after hCG treatment in contrast to PMSG alone and was localized to granulosa cells of preovulatory follicles. Collectively, these data show for the first time that cGK II (not cGK I) and GC-A are selectively induced in granulosa cells of preovulatory follicles by LH- and PR-dependent mechanisms thereby providing a pathway for cGMP function during ovulation.