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)

It is known that nerve growth factor (NGF) induces neurite outgrowth and elevation of the activity of adrenergic marker enzyme, tyrosine hydroxylase (TH) in clonal rat pheochromocytoma cells (PC12), whereas glioma-conditioned medium (GCM) induces neurite outgrowth and elevation of the activity of cholinergic marker enzyme, choline acetyltransferase (ChAT) in PC12 cells. In the previous study we have shown that retinoic acid (RA) induces specific elevation of ChAT activity and depression of TH activity without morphological differentiation (Matsuoka, I. et al., Brain Res., 502 (1989]. In the present study, we compared the effects of NGF, GCM and RA on the intracellular signalings in PC12 cells in relation to the mechanism of cholinergic differentiation. Addition of NGF, GCM or RA to the culture medium of PC12 cells caused a rapid rise in intracellular Ca2+ concentration [( Ca2+]i) reaching the level of almost 2.5-fold the resting condition within 3-18 h. Thereafter, [Ca2+]i of NGF-treated cells were decreased to the resting level within 12 h. On the other hand, [Ca2+]i of GCM-and RA-treated cells decreased to a level which was 1.8- to 2-fold the resting condition within 24-48 h and stayed at this level for up to 4-7 days. When homogenates of GCM- and RA-treated PC12 cells were incubated with [gamma-32P]ATP, phosphorylation of a protein with molecular mass of 27 kDa (27 K-protein) was specifically enhanced. The phosphorylation of the 27 K-protein was not seen in the homogenate of the NGF-treated cells. The phosphorylation of the 27 K-protein was dependent on Ca2+ and inhibited by inhibitors of Ca2+-dependent protein kinase, H-7 and W-7. Addition of H-7 and W-7 to the culture medium of PC12 cells abolished the elevation of ChAT activity specifically induced by GCM and RA. These observations suggested that the sustained increase of [Ca2+]i and Ca2+-dependent protein phosphorylation are involved in the intracellular signaling mechanism required for the cholinergic differentiation of PC12 cells induced by GCM and RA.
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PMID:Possible involvements of intracellular Ca2+ and Ca2+ -dependent protein phosphorylation in cholinergic differentiation of clonal rat pheochromocytoma cells (PC12) induced by glioma-conditioned medium and retinoic acid. 258

The mechanisms of cell proliferative activity regulation under the effect of growth factors, mitogens, virus transformation, etc. were analyzed. Changes in the location of cAMP-dependent protein kinase caused by these factors, the effect of the nerve growth factor on the activities of protein kinase and high-affinity ATPase, and the mechanism of antiproliferative action of staphylococcal enterotoxin A were specified. Data on receptor-independent intracellular penetration of protein factors hydrophobized by fatty acid residues are overviewed.
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PMID:[The main pathogenetic mechanisms of disorders of the detoxication function of the liver in endogenous toxemia of various etiologies]. 262 79

Synthetic peptide substrates specific for cAMP-dependent protein kinase, protein kinase C, ribosomal S6 kinase, and Ca2+/calmodulin-dependent protein kinases were used to monitor regulation of these protein kinases in digitonin-permeabilized PC12 cells following treatment with nerve growth factor (NGF) and epidermal growth factor (EGF). cAMP-dependent protein kinase was not activated by NGF and EGF. In addition, neither the Ca2+/calmodulin-dependent nor -independent activity of a protein kinase similar to Ca2+/calmodulin kinase II was affected by growth factor treatment. However, protein kinase C was rapidly and transiently activated and ribosomal S6 kinase activity was persistently elevated. Maximal protein kinase C activity was observed after 2 to 5 min of treatment and, subsequently, returned to control levels within 30 to 40 min. In contrast, S6 kinase activity was maximal within 15 min of NGF and EGF addition and was stably maintained for at least 24 hr. In addition to protein kinase C and S6 kinase, NGF and EGF regulated a protein kinase that was maximally elevated after 15 to 30 min and returned to control levels within 3 to 5 hr. This kinase (approximately 100 kDa) failed to bind to a calmodulin affinity column and eluted from a cation exchange column as a single major species that was distinct from S6 kinase activity, which eluted as multiple peaks. The findings indicate that at least three protein kinases are rapidly activated in PC12 cells following treatment with NGF and EGF. The distinct durations of activation of each kinase implicates significantly different roles for each in growth factor signalling in PC12 cells.
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PMID:Detection of nerve growth factor and epidermal growth factor-regulated protein kinases in PC12 cells with synthetic peptide substrates. 278 35

We studied the action of bradykinin (BK) on ionic currents in fused pheochromocytoma PC12 cells under voltage-clamp in whole-cell mode, and on intracellular calcium using fura-2 BK induced the development of an outward current associated with an increase in intracellular calcium, followed by inhibition of an M-like current. The outward current was blocked by (+)-tubocurarine, and prevented when the calcium BAPTA or high concentrations of inositol 1,4,5-triphosphate were introduced into the cell, whereas the M-like current and its inhibition by BK remained unaffected. The protein kinase activator phorbol 12,13 dibutyrate partially reduced the M-current. M-current density did not substantially change after prolonged treatment with nerve growth factor.
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PMID:Bradykinin inhibits a potassium M-like current in rat pheochromocytoma PC12 cells. 279 71

The development and survival of spinal motor neurons depends upon muscle-derived trophic factors. Some circumstantial evidence suggested to us that the regulatory subunit of cyclic adenosine 3':5'-monophosphate-dependent protein kinase (cAMP-dPK)-type II might be involved in neuritic outgrowth from spinal neurons. In the present study, we tested a commercial preparation of cAMP-dPK for neurite-promoting activity. Commercial cAMP-dPK-type II from skeletal and cardiac muscles elicited a significant neurite outgrowth from cultured embryonic chicken neurons when the enzyme preparation was bound to polylysine-coated substrata; type I cAMP-dPK from skeletal muscle was ineffective. Neither cAMP-dPK-type I nor -type II had a significant effect on the survival of spinal neurons in culture. Type II cAMP-dPK also stimulated neurite outgrowth from chicken cerebral hemisphere neurons, dorsal root ganglionic neurons, ciliary ganglionic neurons, and rat sympathetic ganglionic neurons in culture. The neurite-promoting activity appears to reside in a contaminant of the preparation since neither the purified regulatory nor catalytic subunits of cAMP-dPK-type II had an effect on neurite outgrowth per se from cultured neurons and since neurite-promoting activity did not correlate with [3H]cAMP binding or cAMP-dependent kinase activity. The neurite-promoting protein was then partially purified from commercial cAMP-dPK-type II by gel filtration on Sephadex G-200 followed by ion-exchange chromatography on DE-52 cellulose. Sodium dodecyl sulfate gel electrophoresis of the active protein peak revealed a major protein band (MW 50 kDa) and several minor bands (e.g., MW 200 kDa, 52 kDa, 45 kDa). Also, immunoblot analysis and immunoprecipitation revealed that the partially purified neurite-promoting protein was distinct from laminin, heparan sulfate proteoglycan, nerve growth factor, neural cell adhesion molecule, and fibronectin. Furthermore, the neurite-promoting activity was not diminished by treatment with heparinase nor was it bound to heparin conjugated to Sepharose. Our results demonstrate that a protein unrelated to laminin or its associated macromolecules and which copurifies with the type II cAMP-dPK of striated muscle stimulates neurite outgrowth from neurons of the central and peripheral nervous systems.
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PMID:A muscle-derived substrate-bound factor that promotes neurite outgrowth from neurons of the central and peripheral nervous systems. 283 49

Protooncogene fos is rapidly and transiently induced by nerve growth factor (NGF) in rat pheochromocytoma PC12 cells. Two adjacent promoter elements have been identified to mediate the NGF response. One element colocalizes with the serum response element (SRE) centered at position -308, previously shown to confer inducibility by serum, phorbol 12-myristate 13-acetate, and epidermal growth factor, whereas the other element, termed SRE-2, maps approximately 20 base pairs downstream of the SRE and contains several sequence repeats. This element also confers serum responsiveness. Gel mobility shift assays have demonstrated that there are specific nucleoprotein complexes associated with each element and that these exist in the cell prior to NGF induction. The NGF response is independent of the cAMP-regulatory element(s) and does not require cAMP-dependent protein kinase II, as induction by NGF is retained in the mutant PC12 cell line A126-1B2. Finally, the human heat shock HSP70 promoter is also transcriptionally activated by NGF and appears to bind the same nuclear complex as the SRE-2 element of the c-fos promoter.
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PMID:Two adjacent promoter elements mediate nerve growth factor activation of the c-fos gene and bind distinct nuclear complexes. 284 7

The role of various intracellular signals and of their possible interactions in the control of neurotransmitter release was investigated in PC12 cells. To this purpose, agents that affect primarily the cytosolic concentration of Ca2+, [Ca2+]i (ionomycin, high K+), agents that affect cyclic AMP concentrations (forskolin; the adenosine analogue phenylisopropyladenosine; clonidine) and activators of protein kinase C (phorbol esters) were applied alone or in combination to either growing chromaffin-like PC12-cells, or to neuron-like PC12+ cells differentiated by treatment with NGF (nerve growth factor). In addition, the release effects of muscarinic-receptor stimulation (which causes increase in [Ca2+]i, activation of protein kinase C and decrease in cyclic AMP) were investigated. Two techniques were employed to measure catecholamine release: static incubation of [3H]dopamine-loaded cells, and perfusion incubation of unlabelled cells coupled to highly sensitive electrochemical detection of released catecholamines. The results obtained demonstrate that: (1) release from PC12 cells can be elicited by both raising [Ca2+]i and activating protein kinases (protein kinase C and, although to a much smaller extent, cyclic AMP-dependent protein kinase); and (2) these various control pathways interact extensively. Activation of muscarinic receptors by carbachol induced appreciable release responses, which appeared to be due to a synergistic interplay between [Ca2+]i and protein kinase C activation. The muscarinic-induced release responses tended to become inactivated rapidly, possibly by feedback desensitization of the receptor mediated by protein kinase C. Muscarinic inactivation was prevented (or reversed) by agents that increase, and accelerated by agents that decrease, cyclic AMP. Agents that stimulate release primarily through the Ca2+ pathway (ionomycin and high K+) were found to be equipotent in both PC12- and PC12+ cells, whereas the protein kinase C activator 12-O-tetradecanoyl-phorbol 13-acetate was approx. 10-fold less potent in PC12+ cells, when administered either alone or in combination with ionomycin. In contrast, the cell binding of phorbol esters was not greatly modified by NGF treatment. Thus control of neurotransmitter release from PC12 cells is changed by differentiation, with a diminished role of the mechanism mediated by protein kinase C.
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PMID:Second-messenger control of catecholamine release from PC12 cells. Role of muscarinic receptors and nerve-growth-factor-induced cell differentiation. 285 Jul 96

The addition of nerve growth factor (NGF) to PC12 cells induces an approximate doubling in the cell surface expression of the Thy-1 glycoprotein and the neural cell adhesion molecule (N-CAM) after 24 h of culture. Although both responses are measured at the same time point, their sensitivity to NGF differed with half-maximal induction of Thy-1 apparent at NGF concentrations (approximately 0.1 ng/ml NGF) that had little effect on N-CAM expression. Phorbol ester derivatives capable of activating Ca2+/phospholipid-dependent protein kinase (protein kinase C) and the calcium ionophore A23187 were found to mimic the NGF induction of Thy-1, but not N-CAM. Similar results were observed when a synthetic diacylglycerol was added to PC12 cell cultures. Increased expression of Thy-1 consequent to phorbol ester, calcium ionophore, or NGF treatment was associated with an increase in the expression of the mRNA species that encodes Thy-1. Increased expression of Thy-1 consequent to all three treatments was also reduced by treatment with the transcription inhibitor cordycepin. Treatment of PC12 cells with high concentrations of phorbol esters was found to inhibit the NGF induction of Thy-1, but not N-CAM. Whereas the above results are consistent with activation of protein kinase C underlying the NGF induction of Thy-1, the same data are not consistent with this pathway being important in the N-CAM response.
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PMID:Comparison of the effects of NGF, activators of protein kinase C, and a calcium ionophore on the expression of Thy-1 and N-CAM in PC12 cell cultures. 289 83

Rat pheochromocytoma (PC12) cells contain specific plasma membrane receptors for both epidermal growth factor (EGF) and nerve growth factor (NGF). Whereas EGF addition to PC12 cells causes a persistent enhancement of proliferation. NGF addition induces a transient stimulation of growth, followed by growth arrest and neuronal differentiation. Despite these differences in biological response, EGF and NGF share a number of early receptor-mediated responses, which are likely te be related to their effect on cell proliferation. In this paper we show that EGF, but not NGF, is able to stimulate the phosphorylation of membrane proteins. In addition, EGF was able to stimulate phosphorylation of a synthetic peptide (RR-SRC) by PC12 membranes in a concentration-dependent manner. Kinetic analysis of the phosphorylation reaction indicated that EGF increased the Vmax from 13 to 70 pmoles/min/mg protein, while no change was observed in Km. Furthermore, EGF was able to stimulate tyrosine phosphorylation of angiotensin I and II, to the same extent as RR-SRC. In contrast no effects of NGF on peptide phosphorylation by PC12 membranes were observed. Cross-linking experiments demonstrated the presence of receptors for both NGF and EGF in PC12 membranes. These different effects of NGF and EGF on activation of membrane-associated protein-kinase activity demonstrate that NGF might be able to stimulate growth transiently without stimulating protein kinase activity.
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PMID:Epidermal growth factor, but not nerve growth factor, stimulates tyrosine-specific protein-kinase activity in pheochromocytoma (PC12) plasma membranes. 300 Apr 61

In previous studies, we observed that the stimulatory effect of (Bu)2cAMP on aromatase activity of human adipose stromal cells was markedly attenuated when fetal calf serum was present in the culture medium. To determine whether growth factors may be the inhibitors of (Bu)2cAMP-stimulated aromatase activity in serum, the effects of growth factors and phorbol esters on aromatase activity of human adipose stromal cells in monolayer culture were investigated. Epidermal growth factor (EGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) were all without effect on aromatase activity when added by themselves, but markedly inhibited aromatase activity stimulated by (Bu)2cAMP. On the other hand, nerve growth factor, multiplication-stimulating activity, relaxin, and insulin had no effect on aromatase activity, either by themselves or in the presence of (Bu)2cAMP. Thus, EGF, PDGF, and FGF can mimic the inhibitory action of fetal calf serum on (Bu)2cAMP-stimulated aromatase activity of these cells. By contrast, none of these substances was capable of mimicking the effect of serum to facilitate the stimulatory action of dexamethasone on aromatase activity of these cells. The phorbol esters phorbol-12-myristate-13-acetate, phorbol-12,13-didecanoate, and phorbol-12,13-diacetate were also capable of facilitating the action of (Bu)2cAMP to stimulate aromatase activity, but had little or no action on dexamethasone-stimulated aromatase activity or when added by themselves. It is concluded that aromatase is under multifactorial regulation in human adipose stromal cells. The activity is induced by glucocorticoids and by agents that stimulate cAMP-dependent protein kinase; the latter effect is potentiated by factors that stimulate protein kinase C, but is suppressed by growth factors such as EGF, FGF, and PDGF, whose actions are believed to be mediated by receptor-linked tyrosine kinase activity.
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PMID:Growth factors suppress and phorbol esters potentiate the action of dibutyryl adenosine 3',5'-monophosphate to stimulate aromatase activity of human adipose stromal cells. 300 2


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