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)

Protein kinase C (PKC) has been implicated in the control of airway smooth muscle (ASM) tone, and abnormalities in PKC-dependent signaling may be associated with asthma. PKC exists in different isoforms, but the pattern of their expression in ASM has not been previously reported. Accordingly, the purpose of the present study was to identify which isoforms of PKC are expressed in ASM. Tissue samples of canine ASM were homogenized and subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, followed by immunoblotting with a range of antipeptide antibodies to PKC-alpha, -beta I, -beta II, -gamma, -delta, -epsilon, -eta, -theta, and -zeta. Positive controls were run in parallel with ASM. Immunoblots revealed a mixture of both calcium-dependent and calcium-independent isozymes: PKC-beta I and PKC-beta II were the only conventional isoforms detected; PKC-delta, PKC-epsilon, and the new muscle-specific isoform, PKC-theta, were all expressed in ASM, but the lung-specific isoform, PKC-eta, was not detected. The calcium- and phospholipid-independent isoform, PKC-zeta, was also present. Thus, expression of a wide variety of both calcium-dependent and calcium-independent isoforms suggests a complex, multifunctional role of PKC in ASM.
Am J Respir Cell Mol Biol 1995 Sep
PMID:Expression of multiple isoenzymes of protein kinase C in airway smooth muscle. 765 81

In the present investigation, we evaluated the roles of calcium, calcium-calmodulin, inositol turnover, and protein kinase C in the release of lipoxygenase-derived metabolites with neutrophil chemotactic activity (NCA) from bronchial epithelial cells (BECs) in response to endotoxin (ETX) and opsonized zymosan (OZ). Both ETX and OZ stimulated BECs to release NCA [56.9 +/- 5.1 (ETX), 65.2 +/- 5.1 (OZ) versus 15.2 +/- 3.0 (controls) cells/high power field, P < 0.001]. The lipoxygenase inhibitors, nordihydroguaiaretic acid and diethylcarbamazine, and phospholipase A2 inhibitors, mepacrine and dibucaine, blocked the release of NCA in response to ETX, OZ, calcium ionophore A23187 (A23187), and phorbol myristate acetate (PMA). The calcium channel blockers, nifedipine and verapamil, and two putative inhibitors of calcium release from intracellular storage sites, 8-(N,N-diethylamine)-octyl-3,4,5-trimethoxybenzoate hydrochloride and ruthenium red, inhibited the release of NCA induced by ETX but had little effect on the release of NCA induced by OZ. However, depletion of extracellular calcium inhibited the release of NCA in response to both ETX and OZ. Calmodulin inhibitors, compound 48/80 and N-(6-aminohexyl)-1 naphthalenesulfonamide (W-7), inhibited the release of NCA in response to a variety of endotoxin concentrations. Lithium chloride, an inositol turnover inhibitor, inhibited the release of NCA in response to both ETX and OZ, but less attenuation was observed in the response to OZ. A protein kinase C inhibitor, dihydrosphingosine, inhibited the release of NCA in response to both ETX and OZ. Finally, A23187 and PMA stimulated the release of NCA and [3H]arachidonic acid independently and additively. These data suggest that the release of NCA from BECs in response to OZ may be predominantly mediated by inositol turnover and protein kinase C and that the release of NCA in response to ETX may be regulated by calcium influx and calcium release from intracellular storage sites, calcium-calmodulin activation, inositol turnover, and protein kinase C activation. Protein kinase C augmented the release of NCA and [3H]arachidonic acid independent of and in combination with calcium. These results may suggest the calcium and protein kinase C dependency of the release of NCA from BECs.
Am J Respir Cell Mol Biol 1995 Sep
PMID:Calcium and protein kinase C dependency of lipoxygenase-derived neutrophil chemotactic activity release from bronchial epithelial cells. 765 91

We recently demonstrated that immortalized GT1-7 neurons co-express luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor and gonadotropin releasing hormone (GnRH) genes. Treatment of GT1-7 neurons with LH/hCG resulted in a transcriptional inhibition of GnRH gene. In the present study, we investigated the signaling and transacting factors involved in the action of hCG. Eight-bromo-cyclic AMP can mimic the down-regulating action of hCG on GnRH mRNA levels. H-89, a protein kinase (PK) A inhibitor, but not bisindolylmaleimide, a PKC inhibitor, blocked the down- regulating actions of hCG as well as of 8-bromocyclic AMP. Treatment with the PKA inhibitor alone modestly decreased GnRH mRNA levels suggesting that PKA signaling also controls the basal expression of the GnRH gene. The direct measurement of PK activities revealed that hCG treatment of GT1-7 neurons increased the PKA but not the PKC activity. New protein synthesis is required for the down-regulating action of hCG on GnRH mRNA levels. Since some of the new proteins could be nuclear transcription or transacting factors, we investigated the effects of hCG on cyclic AMP response element binding protein (CREB), c-Fos and c-Jun protein levels. Treatment of GT1-7 neurons with hCG resulted in an increase of 43 kDa phosphorylated CREB, 50 kDa c-Fos and 40 kDa c-Jun proteins compared to the corresponding controls. The kinetics of increases were different and in all cases the increases of the proteins preceded the decrease of GnRH mRNA levels. In summary, PKA signaling and transacting factors such as CREB, Fos and Jun are probably involved in transcriptional inhibition of GnRH gene by hCG in GT1-7 neurons.
Mol Cell Endocrinol 1995 Apr 01
PMID:Signaling and transacting factors in the transcriptional inhibition of gonadotropin releasing hormone gene by human chorionic gonadotropin in immortalized hypothalamic GT1-7 neurons. 766 77

Androgen (R1881) induced transcriptional activity of the human androgen receptor, stably expressed in CHO cells, can be stimulated an extra 2-fold by the addition of the protein kinase C activator, 4 beta-phorbol 12-myristate 13-acetate (PMA). This extra stimulation is not observed when the protein kinase A activator bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP) is used. The transcriptional activity was measured using a reporter plasmid containing the MMTV-promoter, coupled to the luciferase gene. The effect of PMA on R1881-induced transcription was not due to a higher expression level of the androgen receptor. Also, no extra phosphorylation of the androgen receptor could be measured after incubation with PMA. When GRE-tk-LUC and PSA-LUC reporters were used, the synergistic effect of PMA could not be observed. The findings on the composite MMTV-LTR promoter can be explained by either a direct synergistic interaction between occupied AP-1 like responsive elements and the androgen receptor or via an unknown transcription factor activated by the PKC pathway and interacting with the androgen receptor.
Mol Cell Endocrinol 1995 Apr 28
PMID:Synergism between androgens and protein kinase-C on androgen-regulated gene expression. 767 38

Protein kinase C has been purified from in vitro cultures of A7r5 vascular smooth muscle cells. Three substrates have been employed for the kinetic analysis of the enzyme, Histone III-S, FKKSFKL-NH2 (analogous of the pseudo-substrate of the enzyme) and MBP4-14 (part of basic myelin protein) protein. The enzyme activity depends not only on the PKC-specific sequence motif, common to the three substrates, but also on additional structural motifs, which may be important also in governing the substrate selectivity of the enzyme in vivo.
Biochem Mol Biol Int 1993 Feb
PMID:Purification and kinetic properties of protein kinase C from cultured smooth muscle cells. 768 92

We previously reported that ACTH, but not dibutyryl cAMP, rapidly induces the c-fos proto-oncogene in Y-1 adrenocortical cells. Here we show that PMA induces c-fos with similar kinetics when compared with ACTH (0.5-1 h peak) but reaches only 60% of the maximal ACTH induction and dcAMP is a weak c-fos inducer (15% of ACTH). However, combination of PMA and dcAMP has a synergistic effect leading to maximal c-fos induction. c-fos expression may play a role in the RNA synthesis-dependent corticosteroidogenesis response and/or growth regulation by ACTH. We also show that, in contrast to dcAMP, PMA is a poor steroidogenesis stimulator (15 to 17% of maximum ACTH-stimulated level), its activity being completely dependent on RNA synthesis. Combination of dcAMP and PMA yields an additive steroidogenesis stimulation, an effect that is also dependent on RNA synthesis. Although no strict correlation was found between c-fos induction and early steroidogenesis stimulation, particularly with respect to cAMP derivatives, the results suggest that a PKC pathway is likely to cooperate with the classical cAMP-PKA pathway in adrenal cells' RNA-dependent steroidogenesis.
Mol Cell Biochem 1993 Jul 07
PMID:Relevance of c-fos proto-oncogene induction for the steroidogenic response to ACTH, dcAMP and phorbol ester in adrenocortical cells. 769 73

The action mechanism of gonadotropin-releasing hormone (GnRH) on the cytosolic free calcium concentration ([Ca2+]i) and high-threshold voltage-dependent Ca2+ channel activity was studied in human nonsecreting (NS) pituitary adenoma cells. [Ca2+]i was monitored in individual cells by dual emission microspectrofluorimetry using indo 1 as intracellular fluorescent Ca2+ probe. The whole-cell recording patch-clamp technique was used to study Ca2+ channels. A short application of GnRH (1 to 100 nM) induced an increase in [Ca2+]i due to Ca2+ entry through plasma membrane voltage-sensitive L-type Ca2+ channels. Protein kinase C (PKC) depletion induced by a pretreatment with 1 microM PMA for 24 h abolished spontaneous Ca2+ transients and the action of GnRH on [Ca2+]i and Ca2+ channels. Phloretin (250 microM) and staurosporine (20 nM), two protein kinase C inhibitors, inhibited Ca2+ channel activity, thereby suppressing the effect of GnRH. On the other hand, activation of PKC by a short application of phorbol myristate acetate (10 nM) stimulated Ca2+ influx through Ca2+ channels. These findings demonstrate that, in human NS adenoma cells, GnRH (1 to 100 nM) induces an increase in [Ca2+]i, principally due to Ca2+ entry through L-type voltage-activated Ca2+ channels. PKC regulates this mechanism as well as basal ion channel activity, thus exerting both positive and negative control of [Ca2+]i in stimulated and unstimulated NS adenoma cells.
Mol Cell Neurosci 1994 Dec
PMID:Gonadotropin-releasing hormone induced Ca2+ influx in nonsecreting pituitary adenoma cells: role of voltage-dependent Ca2+ channels and protein kinase C. 770 45

1. To understand better the mechanisms which govern the sensitivity of secretory vesicles to a calcium stimulus, we compared the abilities of injected chromaffin granule membranes and of endogenous cortical granules to undergo exocytosis in Xenopus laevis oocytes and eggs in response to cytosolic Ca2+. Exocytosis of chromaffin granule membranes was detected by the appearance of dopamine-beta-hydroxylase of the chromaffin granule membrane in the oocyte or egg plasma membrane. Cortical granule exocytosis was detected by release of cortical granule lectin, a soluble constituent of cortical granules, from individual cells. 2. Injected chromaffin granule membranes undergo exocytosis equally well in frog oocytes and eggs in response to a rise in cytosolic Ca2+ induced by incubation with ionomycin. 3. Elevated Ca2+ triggered cortical granule exocytosis in eggs but not in oocytes. 4. Injected chromaffin granule membranes do not contribute factors to the oocyte that allow calcium-dependent exocytosis of the endogenous cortical granules. 5. Protein kinase C activation by phorbol esters stimulates cortical granule exocytosis in both Xenopus laevis oocytes and X. laevis eggs (Bement, W. M., and Capco, D. G., J. Cell Biol. 108, 885-892, 1989). Activation of protein kinase C by phorbol ester also stimulated chromaffin granule membrane exocytosis in oocytes, indicating that although cortical granules and chromaffin granule membranes differ in calcium responsiveness, PKC activation is an effective secretory stimulus for both. 6. These results suggest that structural or biochemical characteristics of the chromaffin granule membrane result in its ability to respond to a Ca2+ stimulus. In the oocytes, cortical granule components necessary for Ca(2+)-dependent exocytosis may be missing, nonfunctional, or unable to couple to the Ca2+ stimulus and downstream events.
Cell Mol Neurobiol 1994 Jun
PMID:Evidence that the ability to respond to a calcium stimulus in exocytosis is determined by the secretory granule membrane: comparison of exocytosis of injected bovine chromaffin granule membranes and endogenous cortical granules in Xenopus laevis oocytes. 771 14

Rat liver cytosolic CKII shows heterogeneity resulting from association of the alpha/alpha'-subunits with the beta-subunit or with a phosphorylatable protein of 49 kDa (pp49). Preparations of pp49 were resolved into several spots by two dimensional analysis which might be derived from different degrees of phosphorylation. pp49 was phosphorylated in vitro by purified rat liver CKII and to a lower extent by purified rat brain protein kinase C. In all cases, phosphorylation of pp49 occurred exclusively on Ser. Phosphopeptide maps of phosphorylated pp49 confirmed that the phosphorylation by CKII or PKC takes place in different sites. Prior phosphorylation of pp49 by protein kinase C had no significant influence on the increase of the Km value for beta-casein of CKII, caused by pp49. A tryptic peptide from pp49 has been recently sequenced and antibodies against it had been raised. The antibodies were able to recognize pp49 in rat liver extracts as well as in HL-60 extracts what leads us to presume that this kind of interaction might exist in other species and tissues.
Cell Mol Biol Res 1994
PMID:Protein kinase CKII: possible regulation by interaction with protein substrates. 773 19

The effects of pharmacological agents that interfere with the 1,4,5-inositol trisphosphate (IP3)/diacylglycerol (DAG) pathway on juvenile hormone (JH) biosynthesis by corpora allata (CA) of the cockroach Diploptera punctata have been investigated. These effects were assessed in the presence of the inhibitory neuropeptides, allatostatins, with a view to elucidating the pathway for signal transduction in the inhibition of JH biosynthesis. Treatment of CA with inhibitors of DAG kinase to elevate the concentration of DAG within the CA cells, resulted in a significant, dose-dependent decrease in JH biosynthesis. Simultaneous treatment of glands with both DAG kinase inhibitors and allatostatins further enhanced this effect, suggesting that DAG is an intermediate in the allatostatin-induced inhibition of JH production. The inhibitory actions of the phorbol ester activator of PKC, PDBu, or of allatostatin on JH biosynthesis were partially blocked by pre-incubating the CA with PKC inhibitors. Treatment of CA with the calcium-mobilizing drug thapsigargin resulted in a significant stimulation in JH biosynthesis in glands from mated females producing JH at high rates. Thapsigargin was also able to reverse the effect of allatostatins in high-activity mated CA. This suggests an involvement of the other product of phosphoinositide hydrolysis, IP3, in the modulation of JH biosynthesis at specific developmental times and in glands showing specific levels of activity.
Mol Cell Endocrinol 1994 Oct
PMID:Signal transduction in the inhibition of juvenile hormone biosynthesis by allatostatins: roles of diacylglycerol and calcium. 782 22


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