Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human endometrium normally undergoes a cyclic proliferation process followed by differentiation under the influence of ovarian steroids and locally produced growth and differentiation factors. Understanding of the molecular mechanisms involved in controlling these processes is of great interest, since imbalances between proliferation- and differentiation-promoting signals can have pathophysiological consequences ranging from infertility to endometrial hyperplasia and tumour formation. The present work reviews aspects of the role played by oncogenes and ovarian steroid receptors in modulating proliferation of endometrial tumour cells. The expression pattern and possible roles of protein kinase C (PKC) subunits are discussed in the context of response-specificity of endometrial tumour cells to tumour-promoting agents such as 12-O-tetradecanoyl-phorbol acetate (TPA) and possible implications for anti-tumour therapy.
 ...
PMID:Molecular mechanisms of proliferation in endometrial tumour cells. 1002 5

In the common unidimensional theory of steroid action, steroids bind to intracellular receptors and modulate nuclear transcription and thus protein synthesis. These genomic steroid effects, being characterized by their delayed onset of action and their dependence on transcription and protein synthesis, have been known for several decades. In contrast, very rapid actions of steroids, which are considered to be of nongenomic origin, have been recognized more widely and characterized in detail only during the past ten years. Specific rapid effects of steroids and related hormones like vitamin D3 and thyroid hormones on cellular function involve a conventional second messenger cascade which in most cases includes phospholipase C, phosphoinositide turnover, intracellular pH and intracellular calcium ([Ca2+]i), and protein kinase C. Furthermore, binding sites in membranes have been characterized exposing binding features compatible with an involvement in rapid-steroid signaling. Characteristics of putative membrane receptors are completely different from those of classic intracellular steroid receptors; this also includes the inability of classic steroid receptor antagonists to inhibit those rapid nongenomic steroid actions. The physiological and pathophysiological relevance of these effects is still largely unclear, but their existence has been proven recently even under in vivo conditions. New drugs modulating nongenomic steroid actions may find applications in various areas such as the cardiovascular and central nervous systems, infertility and electrolyte homeostasis. This short review focuses mainly on the nongenomic actions of aldosterone and their cardiovascular implications.
 ...
PMID:Nongenomic steroid actions: completing the puzzle. Aldosterone as an example. 1007 21

Endometriosis, a common gynecological disorder that causes infertility and pelvic pain, is defined as the presence of endometrial glands and stroma within extra-uterine sites. However, despite extensive studies its etiology and pathogenesis are not completely understood. Differentially expressed genes were investigated in epithelial and stromal cells from deep endometriosis and matched eutopic endometrium using cDNA microarrays and laser capture microdissection. Validation of results of several up- and down-regulated genes was performed by quantitative real-time RT-PCR. Our data showed that platelet-derived growth factor receptor alpha (PDGFRA), protein kinase C beta1 (PKC beta1) and janus kinase 1 (JAK1) were upregulated, and Sprouty2 and mitogen-activated protein kinase kinase 7 (MKK7) were downregulated in endometriosis stromal cells, suggesting the involvement of the RAS/RAF/MAPK signaling pathway through PDGFRA in endometriosis pathophysiology. In addition, two potential negative regulators of aromatase expression, chicken ovalbumin upstream promoter transcription factor 2 (COUP-TF2) and prostaglandin E2 receptor subtype EP3 (PGE2EP3), were downregulated in endometriosis epithelial cells, which might result in increased local production of estrogen in endometriosis epithelial cells. Furthermore, three potential candidate genes that might be involved in endometriosis related pain were identified: tyrosine kinase receptor B (TRkB) in endometriosis epithelial cells, and serotonin transporter (5HTT) and mu opioid receptor (MOR) in endometriosis stromal cells were all upregulated. One of the candidate genes, MOR, may be involved in a defective immune system in endometriosis. This study has provided new insights into endometriosis pathophysiology.
 ...
PMID:DNA microarray analysis of gene expression profiles in deep endometriosis using laser capture microdissection. 1529 92

Homozygous Klotho mutant (kl-/-) mice exhibit a variety of phenotypes resembling human aging, including arteriosclerosis, infertility, skin atrophy, osteoporosis, and short life span. Calcium abnormality, one of the phenotypes in kl-/- mice, is thought to be due to the elevated gene expression of 25-hydroxyvitamin D3 1alpha-hydroxylase in the kidney. We studied 25-hydroxy-vitamin D3 1alpha-hydroxylase gene expression using a Klotho plasmid that we had previously constructed for Klotho protein production. It was found that Klotho protein medium upregulated cAMP and the PKC pathway, and suppressed 25-hydroxyvitamin D3 1alpha-hydrox-ylase in kidney cells. However, both cAMP and PKC are known to elevate 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression, therefore, another unknown calcium regulation pathway using Klotho protein medium might exist. Furthermore, we found that activation of the PKC pathway by Klotho was observed only in the kidney and testis, where the Klotho gene is expressed, although activation of the cAMP pathway was observed in any kind of cell. These data suggest that calcium regulation through 25-hydroxyvitamin D3 1alpha-hydroxylase by Klotho depends on non-cAMP and a non-PKC pathway and that the Klotho protein may have different signaling pathways, depending on the Klotho gene expression in different cells and organs.
 ...
PMID:Klotho protein activates the PKC pathway in the kidney and testis and suppresses 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression. 1575 50

HSD-3.8 cDNA (accession number AF311312) encodes a human sperm component. A 0.7 kb fragment (HSD-0.7) containing three immunological epitopes of HSD-3.8 cDNA was prepared and expressed in E. coli. Immunization of female rats with the recombinant HSD-0.7 proteins induced infertility. A cDNA fragment encoding the C-terminal 144 amino acids of human G-protein beta l subunit (Gbeta1-C144) was screened by yeast two-hybrid, when HSD-0.7 segment was used as a bait. Recombinant His6-tagged-Gbeta1-C144 protein was expressed in E. coli BL21 and Anti-Gbeta1 serum was raised with purified Gbeta1-C144. HA-tagged HSD-0.7 and FLAG-tagged Gbeta1 plasmids were constructed and co-transfected into human embryonal kidney 293 cells. Two proteins were localized at superimposable sites in the cytoplasm, and they formed a complex when 500 micromol/L GDP existed. Overexpression of HSD-0.7 activated the G-protein-mediated extracellular signal-regulated kinases (ERK1/2); however, the truncated fragments of HSD-0.7, which lacked either TPR domain or P-loop, lost the ability to activate the ERK1/2 pathway. Further study revealed that the activation of ERK1/2 was protein kinase C (PKC) rather than Ras dependent. These results provide evidence that HSD-3.8 present in spermatocytes and sperm may participate in spermatogenesis and fertilization process by activating the PKC-dependent ERK1/2 signal transduction pathway.
 ...
PMID:A sperm component, HSD-3.8 (SPAG1), interacts with G-protein beta 1 subunit and activates extracellular signal-regulated kinases (ERK). 1636 46

Although the hormone relaxin was discovered 80 years ago, only in the past 5 years have the receptors for relaxin and three other receptors that respond to related peptides been identified with all four receptors being G-protein-coupled receptors. In this review it is suggested that the receptors for relaxin (LGR7) and those for the related peptides insulin-like peptide 3 (LGR8), relaxin-3 (GPCR135), and insulin-like peptide 5 (LGPCR142) be named the relaxin family peptide receptors 1 through 4 (RXFP1-4). RXFP1 and RXFP2 are leucine-rich repeat-containing G-protein-coupled receptors with complex binding characteristics involving both the large ectodomain and the transmembrane loops. RXFP1 activates adenylate cyclase, protein kinase A, protein kinase C, phosphatidylinositol 3-kinase, and extracellular signaling regulated kinase (Erk1/2) and also interacts with nitric oxide signaling. RXFP2 activates adenylate cyclase in recombinant systems, but physiological responses are sensitive to pertussis toxin. RXFP3 and RXFP4 resemble more conventional peptide liganded receptors and both inhibit adenylate cyclase, and in addition RXFP3 activates Erk1/2 signaling. Physiological studies and examination of the phenotypes of transgenic mice have established that relaxin has roles as a reproductive hormone involved in uterine relaxation (some species), reproductive tissue growth, and collagen remodeling but also in the cardiovascular and renal systems and in the brain. The connective tissue remodeling properties of relaxin acting at RXFP1 receptors have potential for the development of agents effective for the treatment of cardiac and renal fibrosis, asthma, and scleroderma and for orthodontic remodelling. Agents acting at RXFP2 receptors may be useful for the treatment of cryptorchidism and infertility, whereas antagonists may be used as contraceptives. The brain distribution of RXFP3 receptors suggests that actions at these receptors have the potential for the development of antianxiety and antiobesity drugs.
 ...
PMID:International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides. 1650 80

The asynchronous secretion of gonadotrope LH and FSH under the control of GnRH is crucial for ovarian cyclicity but the underlying mechanism is not fully resolved. Because prostaglandins (PG) are autocrine regulators in many tissues, we determined whether they have this role in gonadotropes. We first demonstrated that GnRH stimulates PG synthesis by induction of cyclooxygenase-2, via the protein kinase C/c-Src/phosphatidylinositol 3'-kinase/MAPK pathway in the LbetaT2 gonadotrope cell line. We then demonstrated that PGF(2alpha) and PGI2, but not PGE2 inhibited GnRH receptor expression by inhibition of phosphoinositide turnover. PGF(2alpha), but not PGI2 or PGE2, reduced GnRH-induction of LHbeta gene expression, but not the alpha-gonadotropin subunit or the FSHbeta subunit genes. The prostanoid receptors EP1, EP2, FP, and IP were expressed in rat gonadotropes. Incubations of rat pituitaries with PGF(2alpha), but not PGI2 or PGE2, inhibited GnRH-induced LH secretion, whereas the cyclooxygenase inhibitor, indomethacin, stimulated GnRH-induced LH secretion. None of these treatments had any effect on GnRH-induced FSH secretion. The findings have thus elaborated a novel GnRH signaling pathway mediated by PGF(2alpha)-FP and PGI2-IP, which acts through an autocrine/paracrine modality to limit autoregulation of the GnRH receptor and differentially inhibit LH and FSH release. These findings provide a mechanism for asynchronous LH and FSH secretions and suggest the use of combination therapies of GnRH and prostanoid analogs to treat infertility, diseases with unbalanced LH and FSH secretion and in hormone-dependent diseases such as prostatic cancer.
 ...
PMID:Reciprocal cross talk between gonadotropin-releasing hormone (GnRH) and prostaglandin receptors regulates GnRH receptor expression and differential gonadotropin secretion. 1713 45

Styrene is an important industrial chemical that is extensively used in the production of resins, rubbers and fiberglass-reinforced plastics. Exposing male rats to high doses of styrene may produce sperm abnormalities or infertility. To determine the mechanism underlying styrene-mediated toxicity in male reproductive organs, a reverse transcription-polymerase chain reaction (RT-PCR) technology was employed using annealing control primers (ACPs) to identify the differentially expressed genes following styrene treatment in isolated testis of male rats. By using 120 ACPs, a total of 6 expressed sequence tags (ESTs) of genes were differentially expressed in styrene-treated rats, as compared to untreated, which were cloned and sequenced. Of the genes analyzed, 5 genes (testis-specific expressed gene 101, protein kinase C, H+-ATPase isoform 2, peroxiredoxin 1, and aquaporin 9) were inducible and one gene expression (clusterin) was significantly suppressed by styrene. Regulation of each gene by styrene was confirmed by RT-PCR. It was shown that styrene decreased clusterin expression in a concentration-dependent manner and these effects occurred mainly in testis. Taken together, these results indicate that repression of clusterin gene expression by styrene may play an important role in styrene-mediated toxicities.
 ...
PMID:Differential gene expression by styrene in rat reproductive tissue. 1765 43

Hyperprolactinemia is a major cause of infertility, brought about by inhibition of gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus and impairment of luteinizing hormone (LH) output from the pituitary gland. However, whereas the actions of prolactin (PRL) within the brain have been investigated extensively, its specific effects at the level of pituitary gonadotroph target cells remain unclear. Here, we provide evidence that the actions of PRL within the gonadotroph are more complex than originally envisaged. Using a gonadotroph cell monoculture, the first series of experiments showed that PRL is, paradoxically, a potent stimulator of LH release, with a three- to fourfold increase in LH values at hyperprolactinemic concentrations of PRL. Conversely, PRL dose-dependently modulated the LH secretory response to GnRH in a biphasic manner, with classical suppression of LH output only detected under a narrow dose range. In contrast, at all doses tested, PRL blocked the LHB mRNA response to the secretagogue. Subsequent studies revealed that the stimulatory effects of PRL on LH release are not mediated by the conventional cytokine receptor pathways but, rather, by a novel JAK2-PIK3-PKC-dependent signaling cascade. Moreover, the experiments showed that these actions of PRL within gonadotroph cells are controlled by dopamine, the main hypothalamic inhibitory regulator of PRL release in vivo. Our findings have unraveled specific actions of PRL within the gonadotroph and the cell-signaling interactions that ultimately underlie hyperprolactinemia-induced infertility.
 ...
PMID:Characterization of the effects of prolactin in gonadotroph target cells. 2072 Jan 66

A significant decrease in protein kinase C and total sperm count along with increased apoptosis were observed in male Wistar rats exposed to mobile phone frequencies (2 h/day x 35 days at 0.9 W/kg specific absorption rate). The results suggest that a reduction in protein kinase activity may be related to overproduction of reactive oxygen species (ROS) under microwave field exposure. Decrease in sperm count and an increase in apoptosis may be causative factor due to mobile radiation exposure leading to infertility.
 ...
PMID:Mobile phone usage and male infertility in Wistar rats. 2129 41


1 2 Next >>