Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have compared the properties of a rat aorta-derived protein kinase C substrate (p75) with those of 80 kDa kinase C substrates from rat brain (MARCKS) and rabbit aorta (p80). Rat aortic p75 appeared to be closely related to rat brain MARCKS on the basis of: solubility in perchloric acid and trichloroacetic acid, heat stability, isoelectric point (pI approximately 4.2), overall V8 protease phosphopeptide map, and immunocrossreactivity with an antibody directed against the N-terminal domain of MARCKS. However, p75 could be distinguished from rat brain MARCKS and from the rabbit aorta-derived p80 on the basis of its consistently more rapid electrophoretic mobility in SDS-containing gels, and in terms of a unique proteolytic phosphopeptide found in MARCKS but not in aortic p75. We conclude that p75 probably belongs to the family of protein kinase C substrates represented by MARCKS, and that differences in post-translational processing (glycosylation) or mRNA processing may account for the unique properties of the p75 protein in rat aortic tissue.
Mol Cell Biochem 1992 Dec 16
PMID:Comparison of an endogenous protein kinase C substrate in rat aorta with rat brain MARCKS. 133 18

In primary cultures of neurons from cerebral cortex and striatum, 30 s stimulation with the excitatory amino acid glutamate elicited a 5 to 9-fold increase in immediate early gene (IEG) mRNAs. Glutamate increased c-fos, c-jun, jun-B, and NGFI-A (zif/268) mRNAs by binding to both alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor types, and increased c-fos, jun-B, and NGFI-A mRNAs by binding to the metabotropic receptor. NMDA receptor activation elicited IEG expression by a transmembrane calcium influx; AMPA receptor-induced depolarization played a permissive role for the opening of the NMDA receptor channel. The protein kinase C (PKC) inhibitor H-7 (but not inhibitors of cyclic nucleotide-dependent and calcium/calmodulin-dependent protein kinases) partially blocked IEG expression induced by glutamate.
Brain Res Mol Brain Res 1992 Jan
PMID:Differential induction of immediate early genes by excitatory amino acid receptor types in primary cultures of cortical and striatal neurons. 134 32

Using dispersed cultures of fetal rat hypothalami, we studied the effects of forskolin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), activators of protein kinase A and C, respectively, upon vasopressin (VP) secretion, VP mRNA expression and VP mRNA poly(A) tail length. Forskolin stimulated the VP mRNA content and peptide secretion 2.6-fold and induced an increase in the poly(A) tail length of approximately 90 nucleotides. TPA induced an increase in VP mRNA size and stimulated 1.9-fold the secretion of VP without an increase in VP mRNA content. Depolarization with potassium induced an increase in the VP peptide secreted of 2.2-fold, with no effect on the VP mRNA content or size. Increased osmolality had no effect on either VP peptide or VP mRNA. We conclude that VP expression in cultured fetal rat hypothalamic cells is regulated via both protein kinase A and protein kinase C pathways.
Mol Cell Endocrinol 1992 Jul
PMID:Regulated expression of vasopressin gene by cAMP and phorbol ester in primary rat fetal hypothalamic cultures. 135 50

A series of novel gonadotropin releasing hormone (GnRH) and Somatostatin analogs have been developed in our laboratory and were screened for antiproliferative and signal transduction inhibitory effect. Our GnRH analog Folligen, had significant antitumor activity on DMBA induced mammary carcinomas in rats without blocking ovarian functions. The direct effect of Folligen and Buserelin has been compared on the human breast cancer cell line MDA-MB-231. Folligen was found to be more effective in inhibiting cell proliferation and significant differences were found in the signal transduction pathways activated by these analogs. Our novel Somatostatin analogs were screened for tyrosine kinase inhibition and for antiproliferative effect on human colon tumor cells and for growth hormone (GH) release inhibition in vitro and in vivo. The analog TT-2-50 was significantly more active inhibiting GH release in superfused rat pituitary cells and in vivo than native Somatostatin and it strongly inhibited tyrosine kinase and proliferation while it stimulated protein kinase C activity.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Novel antitumor peptide hormones and their effect on signal transduction. 135 11

Cross-resistance to anticancer drugs, termed multidrug resistance (MDR), is functionally associated with the expression of a plasma membrane, energy-dependent, drug efflux pump termed P-glycoprotein (PGP), the product of the mdr1 gene. We have shown previously that MCF-7 breast carcinoma cells transfected with the human mdr1 gene (BC-19 cells) exhibit greater MDR when stably transfected with protein kinase C alpha (PKC alpha). We now demonstrate that transfection of BC-19 cells with the gamma isoform of PKC (BC-19/PKC gamma cells), which is not normally present in BC-19 cells, does not confer increased resistance to doxorubicin, despite a 19-fold increase in PKC activity. All of the increased PKC activity is accounted for by PKC gamma and it is rapidly down-regulated by phorbol dibutyrate, within 15 min of treatment. Endogenous PKC alpha and PKC epsilon activities are not affected by phorbol dibutyrate. The cytotoxicity of doxorubicin was similar in BC-19/neo or BC-19/PKC gamma cells after either 2-hr or continuous drug exposure, and co-treatment with phorbol dibutyrate increased resistance to doxorubicin 4-fold in both cell lines. Phosphorylation of PGP was similar in both cell lines and drug accumulation was not affected by overexpression of PKC gamma. These results demonstrate that transfection of PGP-expressing cells with an atypical isoform of PKC does not confer increased MDR, and they suggest that the regulation of PGP is phenotype specific with respect to the isoform of PKC.
Mol Pharmacol 1992 Dec
PMID:Role of protein kinase C in the modulation of multidrug resistance: expression of the atypical gamma isoform of protein kinase C does not confer increased resistance to doxorubicin. 136 42

In the last decade a great deal of attention was awarded to a signal transduction pathway which is utilized primarily by 'Ca2+ mobilizing' signal molecules and which involves the hydrolysis of a quantitatively minor phospholipid, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) by a PtdIns-specific phospholipase C (PLC). The evidence for the existence of receptor-mediated GTP binding protein-coupled PLC in myocardium and its possible functions are briefly summarized. The minireview is concentrated on the following aspects: 1) cellular localization and synthesis of polyphospho-PtdIns from PtdIns, 2) desensitization of the alpha 1-adrenergic agonist and endothelin-1 mediated PtdIns responses, 3) oscillatory Ca2+ transients initiated by PtdIns(4,5)P2 hydrolysis, 4) polyunsaturated fatty acids as constituents of polyphospho-PtdIns and of the protein kinase C activator 1,2-diacylglycerol (DAG), 5) source other than PtdIns(4,5)P2 contributing to the stimulated DAG, 6) role of the PtdIns pathway in cardiomyocyte growth and gene expression during the hypertrophic response.
Mol Cell Biochem 1992 Oct 21
PMID:Occurrence and functions of the phosphatidylinositol cycle in the myocardium. 136 47

It has been suggested that the therapeutic action of lithium in affective disorders may be due to its inhibition of signal transduction and second messenger synthesis, in particular of the phosphoinositide (PI) pathway. Yet, previous work in neuronal cell lines indicates that lithium has an enhancing effect on gene expression mediated by protein kinase C, which is activated by the PI pathway. In this report, we have analyzed the effect of lithium on two neuropeptide encoding genes that are regulated by second messenger systems; neuropeptide Y (NPY) and proenkephalin (Enk). We find that acute treatment with lithium, resulting in serum levels that are within the therapeutic range effective in patients with mood disorders, significantly enhances basal expression of the NPY gene in rat hippocampus. In contrast, no effect on Enk expression was detected. This selective effect in a limbic structure supports the hypothesis that gene expression may be an important target of lithium's therapeutic action.
Brain Res Mol Brain Res 1992 Jan
PMID:Acute lithium treatment enhances neuropeptide Y gene expression in rat hippocampus. 137 67

Previous work has shown that aggregating fetal brain cell cultures are able to attain a highly differentiated state, and that their development is greatly enhanced by growth and/or differentiation factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and the protein kinase C-activating tumor promoter mezerein. The present study shows that in these 3-dimensional cultures the peptide growth factors EGF and bFGF as well as mezerein are able to induce the expression of the proto-oncogene c-fos. This induction was rapid and transient, in good agreement with observations reported from a wide variety of cell types in vitro. The maximal levels of c-fos mRNA found after stimulation were low in immature cultures and increased greatly as maturation progressed. Of the three factors tested, mezerein was the most potent inducer of c-fos. In contrast to the peptide growth factors EGF and bFGF which were found to induce c-fos only in glial cells, mezerein was stimulatory in glial cells as well as in neurons. A similar cell type specificity has been observed previously for the maturation-enhancing response in immature aggregate cultures. However, in the present study no correlation was found between the degree of c-fos induction and the extent of the maturation-enhancing stimulation. Immature cultures known to be most sensitive and responsive to these maturation-enhancing agents required relatively high doses of peptide growth factors for the induction of c-fos, and the maximal levels of c-fos mRNA elicited were much lower than those in differentiated cultures which did not show any long-term response to these stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1992 Jan
PMID:Expression of the proto-oncogene c-fos in three-dimensional fetal brain cell cultures and the lack of correlation with maturation-inducing stimuli. 137 69

In cultured pituitary gonadotrophs, gonadotropin-releasing hormone (GnRH) caused dose-dependent and biphasic increases in cytoplasmic calcium concentration ([Ca2+]i) and LH release. Both extra- and intracellular calcium pools participate in GnRH-induced elevation of [Ca2+]i and LH secretion. The spike phase of the [Ca2+]i response represents the primary signal derived predominantly from the rapid mobilization of intracellular Ca2+. In contrast, the prolonged phase of the Ca2+ signal depends exclusively on Ca2+ entry from the extracellular pool. The influx of Ca2+ occurs partially through dihydropyridine-sensitive calcium channels. Both [Ca2+]i and LH responses to increasing concentrations of GnRH occur over very similar time scales, suggesting that increasing degrees of receptor occupancy are transduced into amplitude-modulated Ca2+ responses, which in turn activate exocytosis in a linear manner. However, several lines of evidence indicated the complexity over the relationship between Ca2+ signaling and LH exocytosis. In contrast to [Ca2+]i measurements in cell suspension, single cell Ca2+ measurements revealed the existence of a more complicated pattern of Ca2+ response to GnRH, with a biphasic response to high agonist doses and prominent oscillatory responses to lower GnRH concentrations, with a log-linear correlation between GnRH dose and the frequency of Ca2+ spiking. In addition, analysis of the magnitudes of the [Ca2+]i and LH responses of gonadotrophs to a wide range of GnRH concentrations in the presence and absence of extracellular Ca2+, and to K+ and phorbol ester stimulation, showed non-linearity between these parameters with amplification of [Ca2+]i-mediated exocytosis. Studies on cell depleted of protein kinase C under conditions that did not change the LH pool suggested the participation of protein kinase C in this amplification, especially during the plateau phase of the secretory response to GnRH.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Calcium signaling and secretory responses in agonist-stimulated pituitary gonadotrophs. 137 99

An RNA identified by differential cDNA cloning (HAT-2) is highly enriched in canary forebrain in areas associated with the control of complex learned behaviors and higher perceptual processes. The nucleotide sequence predicts a protein that is 96% identical to the product of the n-chimaerin gene isolated from human brain and contains two identifiable domains suggesting a novel role in signal transduction processes. One domain is similar to the sequence in protein kinase C which mediates diacylglycerol binding and regulation. The second domain is similar to a portion of BCR, a GTPase-activating protein encoded by the breakpoint cluster region gene. In male canaries examined during the song season, HAT-2 RNA shows variable expression within the song control circuit, and is notably less abundant in the three nuclei which concentrate androgens (HVC, RA and L-MAN). A fundamental function in the vertebrate forebrain and a possible role in the regulation of neural plasticity are suggested by the conserved structure and pattern of expression of this gene in the brain.
Brain Res Mol Brain Res 1992 Feb
PMID:Differential regulation in the avian song control circuit of an mRNA predicting a highly conserved protein related to protein kinase C and the bcr oncogene. 137 99


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