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)

Rapid changes in morphology of PC12D cells, a subline of PC12 cells, in response to various agents were studied in relation to the subsequent outgrowth of neurites. A few minutes after addition of NGF or of dbcAMP, staining of F-actin with rhodamine phalloidin revealed the formation of ruffles around the periphery of cells. Simultaneous relocalization of F-actin to the area of ruffles occurred in response to NGF. A moderate relocalization of F-actin occurred in dbcAMP-treated cells. Other neurite-promoting agents on PC12D cells, such as bFGF, EGF and PMA, also caused ruffling and an identical redistribution of F-actin. The actin bundles then condensed into several dot-like aggregates that subsequently became the growth cones of neurites. When an inhibitor of protein kinase, K-252a, was added, only the NGF-induced morphological change was selectively decreased. By contrast, an inhibitor of protein kinase A, H-89, selectively blocked the dbcAMP-induced change. These are analogous to the effects of those inhibitors on the outgrowth of neurites. These observations indicate that the formation of ruffles with the redistribution of F-actin might be one of the earliest steps in the neurite outgrowth and that the morphological changes might be triggered by the activation of specific protein kinases. Neither cytochalasin B nor colchicine prevented the series of morphological changes. However, processes formed in the presence of cytochalasin B had no filopodium and protrusions formed in the presence of colchicine were shaped like large filopodia. It appears that microtubules and microfilaments may not be absolutely required for the initiation of the rapid morphological changes, but that complete neurites might be formed with contribution by microtubules and by microfilaments.
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PMID:Requirement for specific protein kinase activities during the rapid redistribution of F-actin that precedes the outgrowth of neurites in PC12D cells. 133 3

As detected by coimmunoprecipitation from PC12 cells, NGF induces rapid association between ERK1 (a growth factor-activated serine/threonine protein kinase) and gp140prototrk NGF receptors. In contrast, no such association is found with the closely related ERK2. Anti-trk immunocomplexes generated from NGF-treated cells also contain protein kinase activity that shares many properties with soluble ERK1. The association of both ERK1 protein and ERK-like kinase activity with gp140prototrk is maximal by 5 min of NGF treatment, persists for approximately 1 hr, and subsequently declines by 18 hr. Treatment with either basic fibroblast growth factor, epidermal growth factor, or orthovanadate also leads to association of ERK1 with gp140prototrk without tyrosine phosphorylation of the latter. The interaction between ERK1 and gp140prototrk may prove relevant to the NGF mechanism.
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PMID:NGF and other growth factors induce an association between ERK1 and the NGF receptor, gp140prototrk. 146 7

Past studies revealed that NGF and fibroblast growth factor (FGF) prevent the death of PC 12 pheochromocytoma cells that otherwise occurs in serum-free medium. Additional agents were tested here for their abilities to promote long-term survival of naive and NGF-pretreated (primed) PC 12 cells in serum-free conditions. Forskolin and permeant cAMP analogs effectively prevented serum-free cell death, as did micromolar levels of insulin and 10-100-nM levels of insulin-like growth factors I and II. In contrast to NGF and FGF, none of these agents caused neuronal differentiation of naive cells or neurite regeneration by primed cells. Each of the agents also prevented rapid cell death in a balanced salt solution, thus apparently ruling out a mechanism dependent on regulation of nutrient uptake. Epidermal growth factor and elevated K+ appeared to slow the rate of cell death, but did not promote long-term survival; phorbol ester, dexamethasone, or vanadate did not prevent cell death. Each of the survival-promoting agents was effective even when macromolecular synthesis was blocked. Because the synthesis inhibitors themselves did not significantly prevent cell death, such findings indicate that survival was promoted by mechanisms that do not require synthesis of RNA or protein. In addition, various lines of experimental evidence (using the kinase inhibitor K-252a or PC 12 cell variants deficient either in protein kinase A activity or in responsiveness to NGF) further suggested that the effective agents maintain survival by independent initial pathways. Regulation of protein kinase activity appears to be a common feature of each pathway and may therefore play a key convergent role in mediating prevention of cell death.
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PMID:Multiple agents rescue PC12 cells from serum-free cell death by translation- and transcription-independent mechanisms. 171 94

Agents that activate cAMP-dependent protein kinase (PKA) as well as agents that increase intracellular calcium induce the expression of certain immediate early genes (IEGs). Recently, it has been demonstrated that the same cis-acting element in the 5' region of the c-fos gene has the ability to mediate both cAMP- and calcium-induced c-fos expression in PC12 cells (Sheng, M., McFadden, G., and Greenberg, M. (1990) Neuron 4, 571-582). Here we demonstrate that both cAMP- and calcium-mediated induction of c-fos and egr1 are dependent on PKA activity. Addition of either depolarizing concentrations of KCl or the calcium ionophore, ionomycin, to PC12 cells increased the expression of both c-fos and egr1, but these inductions were dramatically reduced in three PKA-deficient cell lines, 123.7, AB.11, and A126-1B2. Furthermore, pretreatment of PC12 cells with 20 microM H89, a specific inhibitor of PKA, inhibited forskolin, dibutyryl cAMP, and KCl-induced c-fos and egr1 induction, while having no effect on NGF induction. Likewise, in the PKA-deficient cells, NGF or an activator of protein kinase C induced c-fos and egr1 normally. To determine if PKA deficiency modifies the ability of Ca2+ to activate calcium-dependent kinases, autophosphorylation of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) in response to Ca2+ influx was determined. In parental PC12 cells, PC12 cells pretreated with H89, and PKA-deficient cell lines, CaM kinase was activated equivalently in response to KCl depolarization. These results suggest that PKA is not required for Ca(2+)-induced increase in CaM kinase activity and that the induction of IEGs in response to Ca2+ influx is PKA-dependent. Thus, the requirement for PKA resides at a point distal to the activation of calmodulin-dependent processes.
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PMID:Induction of immediate early genes by Ca2+ influx requires cAMP-dependent protein kinase in PC12 cells. 191 45

The activity of carnitine acetyltransferase (acetyl-CoA:L-carnitine O-acetyltransferase) was found to be at least 50-fold higher than that of choline acetyltransferase in PC12 cells. Nerve growth factor stimulated both enzymes in a parallel manner with respect to concentration of NGF and culture time. The stimulation of both enzymes was completely inhibited by 10 microM 6-thioguanine, an inhibitor of protein kinase N. Results are discussed with reference to the hypothesis that the two enzymes may be functionally related in neuronal cells.
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PMID:Stimulation of carnitine acetyltransferase in PC12 cells by nerve growth factor: relationship to choline acetyltransferase stimulation. 205 39

Tyrosine-specific protein kinase activity in neuronal differentiation was studied in a PC12 pheochromocytoma cell line (PC12-B9) produced by stable transfection with an inducible v-src gene encoding an activated tyrosine kinase (pp60v-src) under the transcriptional control of the mouse metallothionine I gene promoter. Induction of pp60v-src expression with Cd2+ and Zn2+ resulted in the reversible differentiation of PC12-B9 cells into neuron-like cells. pp60v-src elicited morphological differentiation with apparent first order kinetics at the same rate as NGF-directed neurite outgrowth in PC12-B9 cells. v-src gene expression enhanced the rate of NGF-directed neurite extension in an additive manner. Induction of pp60v-src alone constitutively increased the levels of phosphotyrosine-modified proteins (130-120, 90, 83, 65, 60/59, 36 kDa) detected by immunoblotting with phosphotyrosine antibodies. NGF treatment of PC12-B9 cells transiently increased the levels of distinct phosphotyrosine-modified proteins (108, 46, 42 kDa), as well as common substrates, including a 59-kDa protein that comigrated with alpha-tubulin. Phosphotyrosine-modified proteins were not synergistically increased in PC12-B9 cells induced for both v-src and NGF. The nonsynergistic effects of v-src gene expression on neurite outgrowth and phosphorylation suggest that pp60v-src induces PC12 cell differentiation by an intracellular signaling pathway that is largely distinct from that induced by NGF.
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PMID:Neurite extension and protein tyrosine phosphorylation elicited by inducible expression of the v-src oncogene in a PC12 cell line. 207 Aug 24

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 effect of protein kinase modulators on the ability of nerve and fibroblast growth factors to induce neurite outgrowth in pheochromocytoma PC12 cells was studied. The protein kinase inhibitor H7 increased the neurite-stimulating capacity of these factors. The effect of H7 was observed within 1 h and was dose-dependent. HA 1004, an inhibitor of cAMP- and cGMP-dependent protein kinases, did not affect the neurite-stimulating activity of NGF. Substances inhibiting protein kinase C, ganglioside GT1b and quercetin, acted in a similar way whereas sphingosine had an opposite effect.
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PMID:Effect of protein kinase modulators on the induction of morphological differentiation of pheochromocytoma PC12 cells by nerve and fibroblast growth factors. 215 22

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

The rise of the NGF mRNA pool which takes place following exposure of L-929 fibroblasts to serum was prevented in the presence of 5 microM K-252a, a compound which inhibits several species of protein kinase activities. To characterize further this phenomenon, L-929 cells growing in a serum-free medium were exposed to cyclic nucleotide analogs, to a divalent cation ionophore or to the phorbol ester PMA. Only this latter compound induced an enhancement of the NGF mRNA pool, suggesting an involvement of protein kinase C in the upregulation of the NGF transcripts. The effects of PMA or serum also require a synthesis of protein since the level of NGF transcripts remained stable in the presence of cycloheximide.
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PMID:Phorbol 12-myristate 13-acetate (PMA) increases the expression of the nerve growth factor (NGF) gene in mouse L-929 fibroblasts. 231 11


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