scholarly journals Female Fertility Is Reduced in Mice Lacking Ca2+/Calmodulin-Dependent Protein Kinase IV**This work was supported by an NIH Medical Scientist Training Program award (to J.Y.W.) and NIH Grants HD-07503 (to A.R.M.) and HD-1272 (to J.S.R.)

Endocrinology ◽  
2000 ◽  
Vol 141 (12) ◽  
pp. 4777-4783 ◽  
Author(s):  
Joy Y. Wu ◽  
Ignacio J. Gonzalez-Robayna ◽  
JoAnne S. Richards ◽  
Anthony R. Means
Keyword(s):  
Protein Kinase ◽  
Granulosa Cells ◽  
Critical Role ◽  
Follicular Development ◽  
Female Fertility ◽  
Female Reproduction ◽  
Dependent Protein Kinase ◽  
Medical Scientist ◽  
Dependent Protein ◽  
Medical Scientist Training Program

Abstract Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is a serine/threonine protein kinase with limited tissue distribution. CaMKIV is highly expressed in the testis, where it is found in transcriptionally inactive elongating spermatids. We have recently generated mice deficient in CaMKIV. In the absence of CaMKIV, the exchange of sperm nuclear basic proteins in male spermatids is impaired, resulting in male infertility secondary to defective spermiogenesis. The involvement of CaMKIV in female fertility has not been addressed. Here we report that female fertility is markedly reduced in CaMKIV-deficient mice due to impaired follicular development and ovulation. CaMKIV is expressed in the ovary, where it is localized in granulosa cells. We further find that in cultured granulosa cells, CaMKIV expression and subcellular localization are hormonally regulated. As granulosa cells differentiate, CaMKIV levels decrease and the kinase translocates from the nucleus into the cytoplasm. Our results demonstrate a critical role for CaMKIV in female reproduction and point to a potential function in granulosa cell differentiation.

LPS Stimulates Platelet Secretion and Promotes Platelet Aggregation Via TLR4/MyD88 and the cGMP-Dependent Protein Kinase Pathway.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3658-3658
Author(s):  
Guoying Zhang ◽  
Emily Welch ◽  
Asrar B. Malik ◽  
Xiaoping Du ◽  
Zhenyu Li
Keyword(s):  
Platelet Aggregation ◽  
Protein Kinase ◽  
Platelet Activation ◽  
Thrombus Formation ◽  
Critical Role ◽  
Atp Release ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Platelet Secretion

Abstract Bacterial lipopolysaccharide (LPS) induces rapid thrombocytopenia, hypotension and sepsis. Although growing evidence suggests that platelet activation plays a critical role in LPS-induced thrombocytopenia and tissue damage, the mechanism of LPS-mediated platelet activation is unclear. Here we show that LPS stimulated platelet secretion of dense and alpha granules as indicated by ATP release and P-selectin expression, and thus enhanced platelet activation induced by low concentrations of platelet agonists. Platelets express components of the LPS receptor-signaling complex, including Toll-like receptor (TLR4), CD14, MD2, and MyD88. The effect of LPS on platelet activation was abolished by an anti-TLR4 blocking antibody or TLR4 knockout. Furthermore, LPS-induced potentiation of platelet aggregation and FeCl3-induced thrombus formation were abolished in MyD88 knockout mice. Importantly, TLR4 mediates LPS-induced cGMP elevation and the stimulatory effect of LPS on platelet aggregation was also abolished by inhibitors of nitric oxide synthase (NOS) and the cGMP-dependent protein kinase (PKG). Thus, LPS promotes platelet secretion and aggregation through a TLR4/MyD88 and cGMP/PKG-dependent pathway.

scholarly journals Cyclic GMP-Dependent Protein Kinase II Plays a Critical Role in C-Type Natriuretic Peptide-Mediated Endochondral Ossification

Endocrinology ◽  
2002 ◽  
Vol 143 (9) ◽  
pp. 3604-3610 ◽  
Author(s):  
Takashi Miyazawa ◽  
Yoshihiro Ogawa ◽  
Hideki Chusho ◽  
Akihiro Yasoda ◽  
Naohisa Tamura ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Natriuretic Peptide ◽  
Cyclic Gmp ◽  
Endochondral Ossification ◽  
Critical Role ◽  
Dependent Protein Kinase ◽  
Protein Kinase Ii ◽  
Dependent Protein

ACTIVATION INDUCED BY LUTEINIZING HORMONE OF TYPE II PROTEIN KINASE DEPENDENT ON CYCLIC ADENOSINE MONOPHOSPHATE AND PHOSPHORYLATION OF SOLUBLE PROTEINS IN PORCINE GRANULOSA CELLS

1980 ◽  
Vol 84 (1) ◽  
pp. 49-63 ◽  
Author(s):  
D. H. HALPREN-RUDER ◽  
R. A. JUNGMANN ◽  
W. J. GEORGE ◽  
J. R. JETER
Keyword(s):  
Protein Kinase ◽  
Luteinizing Hormone ◽  
Cyclic Amp ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Type Ii ◽  
Dependent Protein Kinase ◽  
Porcine Granulosa Cells ◽  
Dependent Protein ◽  
Dose Dependent

The present experiments were designed to study whether exogenous LH could elicit acute cyclic AMP-mediated activation of cyclic AMP-dependent protein kinase and phosphorylation of cellular protein in intact porcine granulosa cells. Incubation of porcine granulosa cells (from 3 to 5 mm diameter follicles) with 2 μg luteinizing hormone/ml (LH) caused a significant rise of cellular cyclic AMP content within 2 min of the addition of LH. The increase was dose-dependent and occurred between doses of 0·2 and 2·0 μg LH/ml. Luteinizing hormone also caused a time- and dose-dependent dissociation of the type II cyclic AMP-dependent protein kinase isozyme in porcine granulosa cells. Luteinizing hormone (0·05–2 μg/ml) significantly dissociated the cyclic AMP-dependent protein kinase between 2 and 30 min after stimulation. The protein kinase dissociation was a specific effect of LH and was not elicited by either adrenocorticotrophic hormone or prolactin. During the period of LH-induced protein kinase activation, several soluble granulosa cell proteins, ranging in molecular weights from about 43 000 to 99 000, became phosphorylated in a time-dependent and hormone-specific manner. The results suggest that cyclic AMP-mediated activation of granulosa cell type II cyclic AMP-dependent protein kinase may be a prerequisite in the short-term molecular action of LH leading to LH-specific phosphorylation of several soluble granulosa cell proteins of an as yet unidentified function.

scholarly journals Cyclic Guanosine 5′-Monophosphate-Dependent Protein Kinase II Is Induced by Luteinizing Hormone and Progesterone Receptor-Dependent Mechanisms in Granulosa Cells and Cumulus Oocyte Complexes of Ovulating Follicles

2006 ◽  
Vol 20 (2) ◽  
pp. 348-361 ◽  
Author(s):  
Venkataraman Sriraman ◽  
Michael D. Rudd ◽  
Suzanne M. Lohmann ◽  
Sabine M. Mulders ◽  
JoAnne S. Richards
Keyword(s):  
Protein Kinase ◽  
Progesterone Receptor ◽  
Granulosa Cells ◽  
Expression Patterns ◽  
Dependent Protein Kinase ◽  
Pregnant Mare Serum Gonadotropin ◽  
Preovulatory Follicles ◽  
Protein Kinase Ii ◽  
Dependent Protein ◽  
Serum Gonadotropin

Abstract Cyclic GMP (cGMP)-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 pregnant mare serum gonadotropin (PMSG)-human chorionic gonadotropin (hCG)-primed immature mice. Levels of cGK II mRNA were low in ovaries of immature mice, increased 4-fold in response to pregnant mare serum gonadotropin 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 (PR) 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 phorbol 12-myristate 13-acetate enhanced by adenoviral expression of PR-A and blocked by RU486 and trilostane. PR-A in the absence of phorbol 12-myristate 13-acetate 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 pregnant mare serum gonadotropin 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.

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