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

Recent studies have suggested the importance of phosphatidylcholine (PC) metabolism in growth factor-stimulated cells. In these cells, PC is hydrolyzed not only by PC-specific phospholipase C but also by phospholipase D (PLD). In the present investigation, we show that the simple addition of PC-hydrolyzing PLD from Streptomyces chromofuscus to the culture medium of vascular smooth muscle cells elicits choline release into the medium accompanied by the formation of phosphatidic acid. In the presence of ethanol, this treatment elicits a formation of phosphatidylethanol (PEt) at the expense of phosphatidic acid. Furthermore, we show here that exogenous addition of S. chromofuscus PLD induces a marked DNA synthesis in quiescent vascular smooth muscle cells. This DNA synthesis induced by S. chromofuscus PLD is, like platelet-derived growth factor (PDGF)-elicited DNA synthesis, largely dependent on the presence of insulin. In addition, S. chromofuscus PLD-induced PEt formation and DNA synthesis were not affected by protein kinase C down-regulation, whereas PDGF-induced PEt formation and DNA synthesis were significantly inhibited. These observations strongly suggest that protein kinase-dependent activation of PLD is involved in mitogenic signal in PDGF-stimulated cells and that exogenously added PLD acts as a competence factor in the same way as PDGF.
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PMID:Phospholipase D mimics platelet-derived growth factor as a competence factor in vascular smooth muscle cells. 142 2

Cell proliferation and the expression of the protooncogenes c-fos and c-jun have been examined in the primary cultures of oligodendroglial (OL) progenitor cells in response to phorbol 12-myristate 13-acetate (PMA), serum, insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). Combined [3H]thymidine autoradiography and immunocytochemistry was used to assess the mitogenic response of O4 (an oligodendrocyte-specific marker)-positive OL progenitors. In addition, the rate of DNA synthesis was measured by the incorporation of [3H]thymidine into acid-precipitable material. It was found that all of the agents tested stimulated DNA synthesis in OL progenitors and induced a rapid increase in c-fos and c-jun protooncogene expression. The induction of c-fos gene expression and DNA synthesis in response to PMA was completely blocked by 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinase C (PKC), thereby suggesting a role for PKC in the control of c-fos expression and cell proliferation in OL progenitors.
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PMID:Cell proliferation and protooncogene induction in oligodendroglial progenitors. 143 84

Effects of insulin and phorbol esters on subcellular distribution of protein kinase C (PKC) isoforms were examined in rat adipocytes. Both agonists provoked rapid decreases in cytosolic, and/or increases in membrane, immunoreactive PKC-alpha, PKC-beta, PKC-gamma, and PKC-epsilon. Effects of phorbol esters on PKC-alpha redistribution to the plasma membrane, however, were much greater than those of insulin. In contrast, insulin, but not phorbol esters, stimulated the translocation of PKC-beta to the plasma membrane, and provoked changes in PKC-zeta redistribution. Neither agonist altered subcellular distribution of PKC-delta, which was detected only in membrane fractions. Our findings indicate that insulin and phorbol esters have overlapping and distinctly different effects on the subcellular redistribution of specific PKC isoforms.
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PMID:Effects of insulin and phorbol esters on subcellular distribution of protein kinase C isoforms in rat adipocytes. 144 77

The influence of growth factors (GF) and some other biological active molecules on the human bone marrow fibroblast (HBMF) proliferation was studied in the monolayer system. The proliferation of HBMF, like other connective tissue cells, was serum- and GF-dependent. GF tested (EGF, FGF, insulin) produced both positive and negative effects on HBMF proliferation. It was also shown that phorbol ester, which activates protein kinase C, usually inhibited HBMF proliferation. It has been proposed that this feature of HBMF is the cause of GF bifunctional action. It has been suggested that the ability of GF to inhibit HBMF proliferation in some cases permits one to maintain cellular homeostasis in GF rich human bone marrow. HBMF of different hematological patients were characterized by individual differences in GF sensitivity. This may be secondary to the bone marrow cellular composition. For example, HBMF obtained from the bone marrow rich in total cells or megakaryocytes were more responsive to proliferation stimulating effect of GF.
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PMID:[Regulation of fibroblast-like cell proliferation in human bone marrow]. 147 30

GH by means of its sexually differentiated secretory pattern is the predominant regulator of the expression of cytochrome P450 enzymes responsible for a sexual dimorphism of hepatic steroid metabolism. Other hormones, such as gonadal, thyroid and glucocorticoid hormones, as well as insulin appear to modulate the sexually differentiated expression of these enzymes. The major constitutively expressed sex specific forms of P450, belonging to the P4502C-subfamily, have been shown to be regulated by GH at the level of transcription. However, the GH postreceptor events leading to increased or decreased transcriptional activity are essentially unknown. Neither is the functional role of the soluble GH binding protein yet resolved. On-going protein synthesis is a prerequisite for GH transcriptional activation of the female specific P4502C12 but not for all GH effects in the hepatocyte. With regard to signalling mechanisms PKC activity appears to be permissive for the GH induction of P4502C12 but some as yet unidentified factor/kinase(s) may also be activated. The transcriptional control exerted on the rat P4502C-gene subfamily by the pattern of GH secretion offers a versatile tool to elucidate the molecular mechanisms of GH regulation of cytochrome P450 expression.
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PMID:Growth hormone regulation of hepatic cytochrome P450 expression in the rat. 149 21

A number of studies have demonstrated the activation of phospholipase C-mediated hydrolysis of phosphatidylcholine (PC-PLC) both by growth factors and by the product of the ras oncogene, p21ras. Evidence has been presented indicating that the stimulation of this phospholipid degradative pathway is sufficient to activate mitogenesis in fibroblasts as well as that it is sufficient and necessary for induction of maturation in Xenopus laevis oocytes. However, the mechanism whereby PC-PLC transduces mitogenic signals triggered by growth factors or oncogenes remains to be elucidated. In this study, data are presented that show the involvement of protein kinase C zeta subspecies in the channelling of the mitogenic signal activated by insulin-p21ras-PC-PLC in Xenopus oocytes as well as the lack of a critical role of protein kinase C isotypes alpha, beta, gamma, delta, and epsilon in these pathways.
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PMID:Evidence for a role of protein kinase C zeta subspecies in maturation of Xenopus laevis oocytes. 150 83

The hypothesis was tested that the insulin-like effects of Gram-negative bacterial endotoxins (ET), exerted after in vivo administration on subsequently isolated adipocytes, might be associated with changes in protein kinase C (PKC) activity. The latter is believed to be involved in insulin's mechanism of action on adipocytes. E. coli ET was administered to rats either as a bolus injection (1 mg/100 g bw, in 160-180 g rats, LD50 for 6 hr) or via subcutaneously implanted osmotic pumps (0.1 mg/100 g bw/24 hr, for 30 hr, in 340-380 g rats). Control animals received sterile saline. At 6 hr after bolus injection, and at 30 hr after the onset of ET infusion, the animals were sacrificed and epididymal adipocytes isolated. PKC activity and intracellular distribution were assayed after partial purification on DE-52 cellulose minicolumns. Lipogenesis was measured by [3-3H]-D-glucose incorporation into triglyceride. ET treatment by either mode induced a significant increase (76-80%) in PKC activity. PKC intracellular distribution was altered only in chronically ET-treated rats and was expressed as an increased enzyme activity in the membrane fraction. The increased PKC activity was associated with elevated rates of insulin-stimulated lipogenesis only in young rats. We conclude that in young rats, whose adipocytes display high rates of lipogenesis along with elevated insulin sensitivity, PKC is likely to be one of the possible factors involved in mediation of insulin-like effects of ET.
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PMID:Protein kinase C activity and lipogenesis from glucose in isolated adipocytes of endotoxemic rats. 151 1

We have studied the effects of vasopressin and tetradecanoyl phorbol acetate (TPA) on cytosolic free Ca2+ ([Ca2+]i) and insulin release in HIT-T15 beta-cells. Saturable binding of [3H] [Arg8]-vasopressin to HIT cell microsomes indicated a single class of receptors with a dissociation constant (Kd) of 2.5 nM and a total number of binding sites (Bmax) equal to 120 fmol/mg protein. [Arg8]-vasopressin (0.1-100 nM) elicited dose-dependent insulin release from HIT cells by up to 25-fold. This increase was dependent on the presence of extracellular glucose and was blocked by omission of extracellular Ca2+ or addition of verapamil. The stimulation was biphasic; a rapid but short-lived large increase in release was followed by a smaller sustained rise. Vasopressin also evoked a marked, concentration-dependent increase in [Ca2+]i which was also biphasic; an initial spike was followed by a sustained elevation. This increase also required glucose and was blocked by the absence of extracellular Ca2+ or the addition of verapamil. Pretreatment of the cells with TPA overnight to deplete protein kinase C activity did not affect the [Ca2+]i or insulin responses to vasopressin. However, short-term exposure to TPA markedly reduced glucose-induced steady-state [Ca2+]i, despite potentiating glucose-stimulated insulin release sevenfold, and blocked the [Ca2+]i increase induced by vasopressin. These inhibitory effects of TPA were absent in protein kinase C-depleted cells and were prevented by staurosporine. TPA had no significant effect on vasopressin-induced insulin release. Vasopressin did not modify the activity of ATP-sensitive K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of insulin release by vasopressin in the clonal beta-cell line, HIT-T15: the role of protein kinase C. 151 19

There is growing evidence that arachidonic acid (AA) and/or its metabolites may be involved in the control of insulin secretion. We have now investigated the effect of AA on insulin secretion from rat islets, and the possible involvement of protein kinase C (PKC) in this process. Exogenous AA stimulated insulin secretion from intact islets at a substimulatory concentration of glucose (2 mM), but did not further enhance glucose-induced (20mM) insulin secretion. AA-induced insulin secretion was temperature dependent. The secretory responses seen at 37 degrees C were totally abolished by reducing the incubation temperature to less than or equal to 34 degrees C. AA-induced insulin secretion was not dependent upon extracellular Ca2+ and was potentiated by omission of Ca2+ or bovine serum albumin from the media. PKC in rat islets can thus be stimulated by AA, but the stimulation of PKC is not required for AA-induced insulin secretion.
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PMID:Arachidonic acid-induced insulin secretion from rat islets of Langerhans. 151 22

The characteristics of the process by which contraction enhances glucose transport in the frog sartorius were studied. Electrical stimulation increased the permeability of muscles to 3-O-methylglucose (3-O-MeGlc), a nonmetabolizable glucose analogue, increasing efflux as well as uptake. Enhanced efflux was due to an increase in Vmax of the efflux process. A lactacidosis had no effect on basal 3-O-MeGlc efflux, and replacement of media Na+ with Li+ did not affect stimulation-induced uptake. Also, basal and stimulated uptake was not affected by 1 microM 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C activator. Lastly, N-carbobenzoxy-glycyl-L-phenylalaninamide, which inhibits insulin-enhanced, but not basal, glucose uptake in adipocytes, inhibited both basal and stimulated 3-O-MeGlc fluxes in the frog sartorius. From these findings, we conclude: (1) contraction and exercise enhance glucose transport in muscle by increasing the number of transporters in the plasma membrane, or their turnover, by an unknown process; and (2) basal glucose transport of muscle, unlike that of adipocytes, can not be distinguished from stimulated transport on the basis of its insensitivity to N-carbobenzoxyglycyl-L-phenylalaninamide.
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PMID:Stimulation-enhanced 3-O-methylglucose efflux from the frog sartorius: kinetics and properties of the system. 152 Jun 92


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