Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of basic fibroblast growth factor (bFGF) in regulating the functional state of neuropeptide Y (NPY) neurons in the brain was investigated, using aggregate cultures, derived from 17-day-old fetal rat cortex maintained for 16 days in serum-free medium, as a model. The criterion for the functional state was NPY production in response to a 24-h exposure to forskolin + phorbol 12-myristate 13-acetate (For + PMA). bFGF (0.1 nM) induced a approximately 2-fold increase in NPY production under basal conditions as well as after For + PMA (p < 0.001 vs control). To address the possibility that bFGF may interact with other growth factors, we assessed the effect of bFGF in the presence of long R3-insulin-like growth factor-I (l-IGF-I; 1 nM) and found that NPY production in response to For + PMA was even greater than with bFGF alone (2-fold; p < 0.001); even though l-IGF-I by itself was ineffective; suggesting that bFGF is the driving force of this amplification. To assess the selectivity of this process, we evaluated SRIF production in response to For + PMA and found that it was not amplified by bFGF, l-IGF-I, or bFGF + l-IGF-I. These results are consistent with bFGF selectively amplifying the functional state of the cAMP and protein kinase C (PKC) pathways leading to increased NPY-production, with cooperative interaction(s) between bFGF and IGF-I, and with a role for bFGF and IGF-I in the developmental expression/survival of the NPY neurons.
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PMID:Basic fibroblast growth factor selectively amplifies the functional state of neurons producing neuropeptide Y but not somatostatin in cultures of fetal brain cells: evidence for a cooperative interaction with insulin-like growth factor-I. 810 79

A plasminogen activator (PA) system is involved in ovulation, implantation, tumor invasion and metastasis. In order to clarify the regulation of this PA system in endometrial cells, we examined which agent affecting cellular function altered tissue-type plasminogen activator (t-PA) secretion by endometrial carcinoma cell line (KLE cells) in vitro. Triiodothyronine, retinoic acid, insulin, 8-bromo-cAMP, PDGF, IGF-I, basic FGF or TNF-alpha did not alter t-PA secretion while the activator of protein kinase C, phorbol myristate acetate (PMA) stimulated t-PA secretion in a dose-dependent fashion (10(-10)-10(-8) M). The time required to give a statistically significant increase in t-PA over control was 3 hours, and the maximal increase was seen after 24 hours of exposure. Another active phorbol ester, PDD also stimulated t-PA secretion while inactive forms of phorbol ester, 4 alpha-PDD and phorbol did not alter it. Cholera toxin or 8-bromo-cAMP did not affect t-PA secretion, but enhanced PMA-stimulated t-PA secretion. Cycloheximide and actinomycin D completely abolished PMA-stimulated t-PA secretion. These results suggest that (1) t-PA secretion in the endometrial carcinoma cell is modulated by a protein kinase C system, (2) This effect is through new RNA production and protein synthesis. (3) There is a complicated relationship between protein the kinase C and protein kinase A system as to the regulation of t-PA secretion. This would be a suitable model to clarify the PA system in endometrial cells.
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PMID:[Effect of phorbol ester on tissue-type plasminogen activator (t-PA) secretion in endometrial carcinoma cell line in vitro]. 812 84

The data presented in this chapter are summarized in the schematic shown in Figure 9. Insulin binds to and stimulates autophosphorylation of neuronal insulin receptors, whereas, IGF-I and IGF-II binds to and stimulate autophosphorylation of neuronal IGF-I receptors. IGF-II is also capable of binding to the insulin receptor. Whether or not it activates the insulin receptor kinase remains to be clarified. Activated insulin and IGF-I receptor kinases phosphorylate a 70-kDa protein at early times in culture. This protein may mediate some actions of insulin, but we speculate that there are other intermediary proteins involved in the transduction pathway resulting in the activation of S6 kinase and PKC epsilon. The stimulation of S6 kinase by insulin and IGF-I may be associated with the translational activation of protein synthesis by these peptides. The stimulation of PKC epsilon appears to be a necessary step in the transcriptional regulation of the c-fos gene by insulin and IGF-I. The regulation of neuronal protein synthesis at a translational step and the initiation of transcriptional programs regulated by AP-1 represent two mechanisms by which insulin and IGFs alter neuronal growth and differentiation.
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PMID:Insulin and IGF-I receptor signaling in cultured neurons. 821 46

CHO-K1 cells grow in a defined medium with insulin, at physiological concentrations, as the only hormone. IGF-I can substitute for insulin. Quiescent cells require a 9-10-h lag, subsequent to the addition of insulin, to synthesize DNA. The phorbol ester, 12-O-tetradeconoylphorbol 13-acetate (TPA), cannot support growth of these cells, is a more effective inducer than insulin of c-fos, c-myc, c-jun, jun-B, Krox-20, Krox 24, fra-1 and JE, and induces fra-1, JE and c-myc with different kinetics from those of insulin. The addition of insulin + TPA to quiescent cells produces a synergistic effect on DNA synthesis but not on the expression of immediate early genes. Pretreatment of these cells with TPA or insulin decreases the required lag time for DNA synthesis by 3 h in a protein-synthesis-independent manner. These results, together with other experiments, demonstrate that [1] the insulin signal is independent of PKC, [2] insulin acts as a weak competence and a strong progression factor, while TPA behaves as a strong competence factor, and [3] the 9-10-h lag is made up of a 3-h period which is independent of protein synthesis, advancing the cells to a post-G(o) state of 'competence'.
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PMID:The competence progression model in CHO-K1 cells: the relationship between protein kinase C and immediate early gene expression in the insulin mitogenic signal. 832 80

Insulin-like growth factor-II (IGF-II) may be one of the most important local growth factors in human fetal adrenals (HFAs), where its mRNA levels are upregulated by ACTH. We have investigated whether protein kinase C (PKC)-dependent mechanisms and various polypeptide growth factors participate in the regulation of IGF-II gene expression in cultured HFA cells, and whether HFA cells secrete IGF-II peptide into the culture medium. ACTH enhanced IGF-II mRNA accumulation dose- and time-dependently, maximally four- to sixfold, and this increase was inhibited dose-dependently (0.01-100 micrograms/l) by 12-O-tetradecanoyl phorbol-13-acetate (TPA), a PKC activator. TPA decreased basal IGF-II mRNA levels by approximately 55%. Staurosporine, a PKC inhibitor, abolished the inhibitory effects of TPA and induced accumulation of IGF-II mRNA. Dibutyryl cyclic AMP, cholera toxin and forskolin increased IGF-II mRNA accumulation as much as ACTH, and TPA inhibited these stimulations in a similar way. ACTH increased the IGF-II peptide concentration in most experiments, but this increase was modest in comparison with IGF-II mRNA changes. TPA, although it decreased IGF-II mRNA levels, tended to increase IGF-II peptide in the medium. Additions of GH, IGF-I and IGF-II to the cell culture medium also increased IGF-II mRNA accumulation. Transforming growth factor-beta 1 inhibited IGF-II mRNA accumulation to the same extent as TPA. Epidermal growth factor and basic fibroblast growth factor did not change IGF-II mRNA levels. Our results confirm previous reports that ACTH is an important regulator of IGF-II in human fetal adrenals, and show that IGF-II gene expression is under multifactorial control, which includes the PKC system and polypeptide growth factors.
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PMID:Insulin-like growth factor-II in human fetal adrenals: regulation by ACTH, protein kinase C and growth factors. 839 23

A clonal hepatocyte line (FMH-202-2), derived from livers of fetal transgenic mice harbouring human growth hormone (hGH) and SV40 T antigen as transgenes, was used in the investigation of protooncogene expression involved in liver-specific growth control and/or in hepatocellular transformation. In this model system, representing an immortalized, yet untransformed phenotype, the transgenes hGH and SV40 T antigen were expressed constitutively. The c-fos protooncogene was induced by incubation with insulin, epidermal growth factor (EGF) and insulin-like growth factor (IGF-I) in a transient manner comparable to its expression in primary murine hepatocytes. Elucidation of second messenger mechanisms demonstrated that c-fos induction by hepatotrophic growth factors was not mediated by protein kinase C. In contrast to primary hepatocytes, the c-myc protooncogene exhibited a constitutive expression pattern which was independent of growth factor stimulation. These results indicate that apart from hGH and SV40 T antigen, c-myc may play a role in cellular immortalization, but that constitutive expression of these genes, even in combined coexpression, does not suffice to induce the transformed phenotype.
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PMID:Expression of c-fos and c-myc protooncogenes in an immortalized hepatocyte line harbouring SV40 T antigen and hGH as transgenes. 851 38

The abilities of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-I) to regulate cAMP metabolism and mitogen-activated protein kinase (MAP kinase) activity were compared in human arterial smooth muscle cells (hSMC). PDGF-BB stimulated cAMP accumulation up to 150-fold in a concentration-dependent manner (EC50 approximately 0.7 nM). The peak of cAMP formation and cAMP-dependent protein kinase (PKA) activity occurred approximately 5 min after the addition of PDGF and rapidly declined thereafter. Incubating cells with PDGF and 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor) enhanced the accumulation of cAMP and PKA activity by an additional 2.5-3-fold, whereas IBMX alone was essentially without effect. The PDGF-stimulated increase in cAMP was prevented by addition of the cyclooxygenase inhibitor indomethacin, consistent with release of prostaglandins stimulating cAMP. PDGF, but not IGF-I, stimulated MAPK activity, cytosolic phospholipase A2 (cPLA2) phosphorylation, and cAMP synthesis which indicated a key role for MAP kinase in the activation of cPLA2. Further, PDGF stimulated the rapid release of arachidonic acid and synthesis of prostaglandin E2 (PGE2) which could be inhibited by a cPLA2 inhibitor (AACOCF3). Calcium mobilization was required for PDGF-induced arachidonic acid release and PGE2 synthesis but not for MAPK activation, whereas PKC was required for PGE2-mediated activation of PKA. In summary, these results demonstrated that PDGF increases cAMP formation and PKA activity through a MAP kinase-mediated activation of cPLA2, arachidonic acid release, and PGE2 synthesis in human arterial smooth muscle cells.
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PMID:Platelet-derived growth factor stimulates protein kinase A through a mitogen-activated protein kinase-dependent pathway in human arterial smooth muscle cells. 855 Jun 11

Tyrosine kinases are involved in cell signalling of growth factors such as insulin and insulin-like growth factor (IGF-I) and others. Insulin and IGF-I receptors which possibly feedback on insulin release are established in insulin-secreting cells. The role of tyrosine kinase in insulin secretion is controversial. Both the tyrosine kinase inhibitors tyrphostin 25 (TYR) and genistein (GEN), but not its structurally similar albeit biologically inactive analogue daidzein, increase insulin release at 16.7 mM glucose in INS-1 cells, an insulin secreting cell line. Tyrosine kinase activity is inhibited by GEN, but not diadzein. The inhibitory effects of either insulin or IGF-I on insulin release are abolished by 10(-4) M GEN but not by daidzein indicating an involvement of tyrosine kinase in the inhibitory effect of both insulin and IGF-I on insulin release. Since GEN was argued not to be specific for tyrosine kinase, several second messengers were investigated. cAMP is not influenced. The insulinotropic effect of acutely administered TPA is not influenced by GEN while in protein kinase C (PKC)-downregulated cells the insulinotropic effect of GEN is preserved: both indicate no involvement of PKC in GEN effect. Since pertussis toxin (PT) pretreatment has no effect on the inhibitory effects of IGF-I on insulin release, a PT-sensitive G-protein is not likely to be involved. The data indicate that tyrosine kinase is involved in the inhibitory effects of insulin and IGF on insulin release in INS-1 cells, possibly mediating the negative feedback effect.
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PMID:Role of tyrosine kinase in insulin release in an insulin secreting cell line (INS-1). 856 11

The regulation mechanism of glucose transporter 1 (GLUT1) gene expression was investigated in cultured bovine corneal endothelial cells. Epidermal growth factor (EGF) stimulated both GLUT1 mRNA expression and cell proliferation. Fetal bovine serum, in contrast, stimulated cell proliferation but did not increase GLUT1 mRNA. IGF-I, hyaluronic acid or fibronectin did not stimulate GLUT1 gene expression. These results suggest that GLUT1 gene expression is controlled, at least in part, by EGF and is related to neither cell proliferation, cell motility nor cell adhesion regulation. The EGF signal was transduced through a pathway including protein kinase C. GLUT1 is reported to work as a water transporter, and so EGF can be considered as one of the possible agent which stimulate water transport activity through the corneal endothelial cells. EGF could be useful in the therapy of corneal edema caused by endothelial dysfunction.
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PMID:Regulation of glucose transporter 1 (GLUT1) gene expression by epidermal growth factor in bovine corneal endothelial cells. 857 72

We have recently demonstrated the existence of an autocrine growth loop driven by platelet-activating factor (PAF) in the human endometrial adenocarcinoma. cell line HEC-1A. To investigate a possible cooperation between PAF and the insulin-like growth factor (IGF) system in this cell line, the effect of PAF on insulin-like growth factor binding protein (IGFBP) production as well as binding and biological activities of IGF-I, IGFv-II, and the analog Des(1-3)IGF-I have been evaluated. Analysis of self- and cross-displacement curves of [125I]IGF-I binding to HEC-1A cells indicates the presence of a single class of binding sites, with affinity constants of 1-4 nM for IGF-I and IGF-II and 70 nM for Des(1- 3)IGF-I, which binds to IGFBPs with lower affinity. Insulin does not apparently bind to this binding site. Moreover, the addition of increasing concentrations of IGF-I leads to a paradoxical increase of binding. These results indicate a similarity of this binding site to IGFBPs. The presence of IGFBPs has been demonstrated by Western ligand blot analysis of HEC-1A conditioned medium which shows the presence of two bands of 32-34 and 40-45 kDa. By Western immunoblotting analysis, the two bands were respectively identified as IGFBP-2 and IGFBP-3. Incubation with PAF (1 microM) highly increases the release of the two IGFBPs from the cells. Such an effect is inhibited by the PAF receptor antagonist L659,989, by the PKC inhibitor sangivamycin, and by the tyrosine kinase inhibitor genistein. PAF also induces a time-dependent increase of mRNA expression for IGFBP-3, suggesting an effect on synthesis of this protein. IGF-I and IGF-II (0.1-100 nM) are almost ineffective in inducing [3H]thymidine incorporation, whereas a slight proliferative effect is observed with Des(1-3)IGF-I which also increases PAF synthesis. These data demonstrate a modulatory action of PAF on IGFBP secretion in HEC-1A cells and indicate that the IGF system plays a minor, if any, modulatory role on proliferation of this cell line.
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PMID:Platelet-activating factor enhances production of insulin-like growth factor binding proteins in a human adenocarcinoma cell line (HEC-1A) 864 11


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