Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In dog thyroid cell primary cultures the prolonged presence (up to 4-6 days) of TSH induced down regulation of the isoenzyme I (PKA I) of cAMP-dependent protein kinases. In the simultaneous presence of TSH and EGF this down regulation of PKA I was maintained, although it was slightly smaller than in assays without EGF. In contrast, the simultaneous presence of TPA, totally inhibited the TSH induced down regulation of PKA I. These results partly explain the previously observed additivity of TSH and EGF, and the non-additivity of TSH and TPA actions on cell proliferation in these cells.
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PMID:Epidermal growth factor and phorbol ester actions on the TSH induced down regulation of the isoenzyme I (PKA I) of cyclic AMP-dependent protein kinases in dog thyroid cell primary cultures. 187 89

The BeWo cell line, derived from choriocarcinoma, produces and releases human chorionic gonadotropin (hCG) and its alpha- and beta-subunits. The authors have already reported that cAMP and EGF stimulated the production and secretion of hCG and its subunits by cultured BeWo cells. Therefore, in order to elucidate the role of signal transduction systems (cAMP-A-kinase system, DG-C-kinase system and Ca(2+)-calmodulin system) in the regulation of hCG (alpha, beta) synthesis by human choriocarcinoma cells, effects of cholera toxin (CT), an activator of adenylate cyclase, phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, and Ca2+ ionophore A23187, an activator of Ca2+ modulation on hCG (alpha, beta) production and secretion by BeWo cells cultured in a serum-free condition were evaluated. Immunoreactive hCG alpha, hCG beta and hCG in the media and cultured cells were measured by each homologous RIA for hCG alpha, hCG beta and hCG, respectively. Addition of CT at a concentration of 100 ng/ml into the medium caused extreme increases in the cellular levels of hCG alpha, hCG beta and hCG together with remarkable increases in hCG alpha, hCG beta and hCG levels in the medium. This stimulatory effect of CT was first observed on the increase of hCG alpha levels in cultured BeWo cells and medium at 3h, then observed on the increase of hCG beta levels at 6h and was last detectable on the increase of hCG levels in the cultured cells and medium at 12h. Addition of PMA at a concentration of 100 ng/ml into the medium caused an increase in the cellular and medium levels of hCG alpha, hCG beta and hCG shortly (3h) after the exposure to PMA. Addition of A23187 at a concentration of 100 ng/ml into the medium caused a slight increase in hCG alpha levels in the medium at 6h without accompanying the increase in those cellular levels. When added together, PMA potentiated the stimulatory effect of CT on hCG alpha, hCG beta and hCG levels in the cultured BeWo cells and medium, while PMA did not potentiate the effect of A23187 in this experimental condition. These findings suggest that cAMP-A-kinase system plays a major role in the signal transduction of hCG (alpha, beta) synthesis and secretion by BeWo choriocarcinoma cells, and that DG-C-kinase system interacts synergistically with cAMP-A-kinase system in the regulation of hCG (alpha, beta) synthesis and secretion by BeWo cells. Ca(2+)-calmodulin system appears to participate in the regulation of hCG alpha secretion without affecting the synthesis of hCG (alpha, beta) in BeWo cells.
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PMID:[The role of signal transduction systems in the regulation of the production and secretion of hCG (alpha, beta) by cultured human choriocarcinoma cells (BeWo)]. 188 9

The EGF receptor (EGF-R), a 170 KD transmembrane glycoprotein, is found at a high level in the BT20 human mammary carcinoma cell line (1 +/- 0.4 x 10(6) sites per cell). In this study, we examined the expression of the EGF-R gene in BT20 cell line by in situ hybridization at the light and electron microscopic level using a human cDNA, corresponding to EGF-R transmembrane and protein kinase domains, labeled with [3H]-, [35S]-, or [32P]-d-ATP. Two treatments were tested to embed cells in Lowicryl resin: the first used fixation and dehydration by progressive lowering of temperature, the second quick freezing and cryosubstitution. The best ultrastructural preservation was obtained with the second procedure without modification of the hybridization signal. EGF-R mRNA was observed principally at the cytoplasmic level, on organelles involved in the protein synthesis process. Labeling was also located on the microvilli which extend into the intercellular space, suggesting that some mRNA would be located in sites where EGF-R is utilized. Some mRNA was observed in the nucleus. This study demonstrates that post-embedding in situ hybridization, after quick freezing and cryosubstitution, is a powerful EM in situ hybridization procedure to study the expression of the EGF-R gene.
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PMID:Ultrastructural localization of mRNA encoding for the EGF receptor in human breast cell cancer line BT20 by in situ hybridization. 198 69

Tissue-type plasminogen activator (tPA) is secreted by rat granulosa cells in response to treatment with activators of protein kinase A (follitropin, FSH), protein kinase C (gonadotropin-releasing hormone, GnRH) and tyrosine kinase (epidermal growth factor, EGF). Because steroid hormones have been shown to enhance the gonadotropin stimulation of ovarian differentiation, we investigated the effects of steroid hormones, alone or together with various kinase activators, on tPA activities and mRNA levels in cultured rat granulosa cells. Treatment of cells with dexamethasone (DEX; a glucocorticoid agonist) or R1881 (an androgen agonist) caused an increase in tPA secretion and mRNA levels. In addition, the stimulation of tPA activity and mRNA levels by FSH (50 ng/ml) was synergistically enhanced by cotreatment with DEX or R1881 in a time-dependent manner with 2.8- and 1.6-fold increase at 9 h after incubation as compared to cells treated with FSH alone. In contrast, treatment with diethylstilbestrol had no effect on tPA levels. Furthermore, tPA activity and mRNA levels induced by GnRH and EGF were also increased by cotreatment with DEX or R1881 as compared with cells treated with GnRH or EGF alone. Likewise, the stimulation of tPA mRNA levels by dibutyryl cAMP, a protein kinase A activator, and phorbol myristate acetate (PMA), a protein kinase C activator, was enhanced by cotreatment with DEX or R1881. These results demonstrate that glucocorticoid and androgen enhance tPA secretion and mRNA levels stimulated by FSH, GnRH and EGF in granulosa cells. The rat granulosa cells provide a useful model for studying the mechanism of regulation of tPA gene expression by steroid hormones.
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PMID:Synergistic effect of glucocorticoids and androgens on the hormonal induction of tissue plasminogen activator activity and messenger ribonucleic acid levels in granulosa cells. 210 7

The mature product of the c-met proto-oncogene is a putative tyrosine kinase receptor of 190 kd with an alpha beta heterodimeric structure. The c-met protein is phosphorylated in vivo on the beta subunit in the gastric carcinoma cell line GTL-16 (Giordano et al., 1988). Western blots with phosphotyrosine antibodies show that tyrosine phosphorylation of the beta subunit is reduced by treatment of GTL-16 cells with protein kinase C activators (tumor promoting phorbol esters such as phorbol 12-myristate 13-acetate, TPA, and beta-phorbol 12,13-dibutyrate, PdBu, or membrane permeable synthetic diacylglycerol 1-oleyl-2-acetyl-sn-glycerol, OAG). The inactive analog alpha-phorbol 12,13-didecanoate has no effect. The inhibition induced by TPA is dose dependent and maximal after 1 h. Depletion of protein kinase-C by prolonged treatment with TPA (18-48 h) increases the phosphorylation on tyrosine of the beta subunit. Phospho-amino acid analysis of the c-met protein immunoprecipitated from [32P]orthophosphate-labelled GTL-16 cells shows that protein kinase-C activation leads to an increase in serine phosphorylation and to concomitant decrease in tyrosine phosphorylation. These results suggest that, similar to the EGF and insulin receptor, the putative receptor encoded by the c-met proto-oncogene may be negatively modulated by protein kinase-C phosphorylation.
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PMID:Protein kinase-c activation inhibits tyrosine phosphorylation of the c-met protein. 211 5

We have studied factors controlling message levels for the neuronal growth- and plasticity-associated protein, GAP-43. Following exposure of PC12 cells to various effectors, cytoplasmic RNA was isolated and analyzed by Northern transfer and autoradiography using a GAP-43 cDNA probe. Induction by NGF is apparent after 3 hr exposure and reaches maximal levels at 24 hr. Beyond 24 hr, levels remain constant in the continued presence of NGF. Induction is insensitive to variations in culture conditions, such as plating density or substrate, which influence NGF-induced neurite outgrowth. Other inducers, in order of decreasing efficacy, are FGF, dBcAMP, TPA, K+, and EGF. Insulin and retinoic acid are ineffective. Dexamethasone partially inhibited basal expression as well as induction by NGF, FGF, dBcAMP, and TPA. The methyltransferase inhibitor 5'-S-(2-methyl-propyl)adenosine completely inhibited induction by NGF, FGF, and dBcAMP. Inhibition of protein synthesis by cycloheximide partially decreased induction by NGF, FGF, and TPA but slightly enhanced dBcAMP induction. Complete down-regulation of protein kinase C by chronic TPA treatment completely eliminated the TPA response but slightly enhanced induction by NGF. These findings and the results of additivity experiments in which cells were stimulated with various combinations of NGF, dBcAMP and TPA suggest that NGF induction of GAP-43 RNA (1) does not involve activation of protein kinase C but (2) may be mediated partially via activation of protein kinase A.
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PMID:Factors influencing GAP-43 gene expression in PC12 pheochromocytoma cells. 213 63

The regulation of cellular growth and proliferation is perhaps the most investigated and elusive problem in cell biology and seems to be possible to solve from almost any angle of study chosen. Among the non-systemic factors that have been discussed are genetic damage, genomic control, regulation by stimulatory and inhibitory peptide factors such as EGF, chalones, and fibronectin, protein kinase activation with tyrosine phosphorylation, adenylylcyclase and cAMP, cGMP, membrane perturbations and specifically in tumours the failure of the Pasteur effect in control of glycolysis, excessive membrane ATPase activity, and excessive hydrolytic and proteolytic activities at the cell surface. This article focuses on the central role of fluxes within the plasma membrane and re-examines the possibility that changes of flux of metabolites, ions, and reducing equivalents may be the common denominator regulating cellular proliferation.
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PMID:A unifying model of the cell proliferation emphasizing plasma membrane fluxes. 214 43

PC-12 pheochromocytoma cells contain a growth factor-sensitive protein kinase that phosphorylates microtubule associated protein 2 (MAP-2). This MAP kinase is also activated by the protein phosphatase inhibitor okadaic acid (OA). Additionally, OA potentiates the NGF-dependent activation of MAP kinase, but causes only a modest potentiation (20%) of the maximal activation observed with EGF. Since OA is a specific serine/threonine phosphatase inhibitor, these results suggest that serine/threonine phosphorylation may be involved in the hormonal regulation of MAP kinase.
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PMID:Okadaic acid stimulates the activity of microtubule associated protein kinase in PC-12 pheochromocytoma cells. 216 Dec 19

Ligand stimulation of the platelet-derived growth factor receptor (PDGF-R) results in rapid activation of the receptor tyrosine kinase, stimulation of phosphoinositide hydrolysis, an increase in intracellular free Ca2+ concentration ([Ca2+]i), and, ultimately, cellular proliferation. In a previous study, we demonstrated that staurosporine, a known inhibitor of protein kinase C, blocked PDGF-induced [Ca2+]i increases in Swiss mouse 3T3 fibroblasts by a mechanism that appeared unrelated to inhibition of protein kinase activity (Olsen, R., Melder, D., Seewald, M., Abraham, R., and Powis, G. (1990) Biochem. Pharmacol. 39, 968-972). In the present study, we report that staurosporine inhibits ligand-dependent PDGF-R tyrosine kinase activation in cell-free receptor preparations and in intact Swiss 3T3 cells. At the same concentrations (10(-8)-10(-6) M), staurosporine suppressed both the tyrosine phosphorylation of phospholipase C activity and the hydrolysis of phosphoinositides induced by PDGF stimulation of intact cells. In contrast, guanine nucleotide-binding protein-dependent phospholipase C activation induced by bradykinin or fluoroaluminate anion was relatively insensitive to staurosporine. A preferential inhibitory effect of staurosporine on signal generation by the PDGF-R was indicated by findings that epidermal growth factor receptor (EGF-R) tyrosine kinase activity and EGF-dependent phospholipase C in A-431 carcinoma cells were approximately 100-fold less sensitive to this drug. These data indicate that submicromolar concentrations of staurosporine inhibit PDGF-dependent phosphoinositide hydrolysis and Ca2+ mobilization through a proximal inhibitory effect on ligand-induced activation of the PDGF-R tyrosine kinase.
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PMID:Preferential inhibition of the platelet-derived growth factor receptor tyrosine kinase by staurosporine. 217 5

We have previously shown that EGF promotes growth and proliferation of enterocytes isolated from the crypts of the rat small intestine (IEC-6). In the present studies we have measured the affinity of EGF for its receptor, and estimated the number of surface EGF receptors on IEC-6 cells. Scatchard analysis indicates IEC-6 cells display 45,000 EGF receptors per cell with a dissociation constant of 41 pM. Treatment with phorbol-12-myristate-13-acetate (PMA) results in a dose-dependent inhibition of cell growth which is paralleled by reduced binding of 125I-EGF. Incubation of IEC-6 cells with 10 nM PMA results in a 70 percent decrease in the number of EGF receptors without a significant change of receptor affinity (kd 68 pM vs 41 pM). PMA treatment is also associated with a significant increase of protein kinase-C activity in IEC-6 cells. The reciprocal relationship between protein kinase-C activation and EGF receptors suggests in this cell line of crypt enterocytes, protein kinase-C may inhibit cellular proliferation by modulating EGF receptors.
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PMID:Modulation of EGF-receptors by phorbol ester in small intestinal crypt cells. 232 19


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