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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The induction of T cell proliferation and differentiation into mature effector cells is dependent on two principal exogenous signals that are provided by the antigen or mitogen and IL2. The enzyme protein kinase C (PKC) has a major role in the antigen-receptor signalling pathway in T cells, but appears not to be involved in signalling via the IL2-receptor (IL2-R). Since both pathways trigger a series of sequentially coordinated transcriptional events in which numerous genes are activated, we tested whether a T cell mitogen acting via the TCR/CD3 complex, and IL2, affect the expression of the conventional, Ca(2+)-dependent, PKC genes (alpha, beta and gamma) in T cells. Stimulation of human peripheral blood lymphocytes or an enriched population of human T cells with phytohemagglutinin resulted in augmented mRNA levels of PKC alpha and PKC beta, but not PKC gamma-gene. The response peaked at 24-48 hr when a 3-5-fold increase was observed. Stimulation of IL2-R alpha-expressing T cells with human recombinant IL2 induced cell proliferation and transcription of the IL2-R alpha gene (greater than 100-fold), but did not change mRNA levels of PKC alpha or PKC beta genes. The results suggest that stimulation of human T cells with mitogens acting via the TCR/CD3 complex, that involve activation of PKC, is accompanied also by a late activation of selected PKC genes. By contrast, agonists such as IL2, that operate via a different signalling pathway, do not modify the expression of any of the known conventional PKC genes.
Mol Immunol
PMID:Mitogen-induced human T cell proliferation is associated with increased expression of selected PKC genes. 163 62

We have studied the activity and the phorbol-binding capacity of protein kinase C (PKC) in subcellular fractions, as well as the relative amount of the enzyme protein in rat livers reperfused after severe nonnecrogenic ischemia. Ischemia causes a significant decrease in PKC phosphotransferase activity in both membranes and cytosol which lasts long after the reestablishment of the blood flow. The phorbol-binding capacity of the membrane fraction shows the same behavior. The amount of PKC protein decreases during ischemia (-25%) but returns to normal after reperfusion more promptly than activity and binding capacity, suggesting that PKC resynthesized in postischemic livers is either functionally defective or incapacitated by unsuitable conditions of the environment. We have also measured the contents of some lipids that may influence PKC activity in the cell. During ischemia and reperfusion there is a significant increase in the content of 1,2-diacylglycerol (DAG), which is the physiological activator of PKC, but under the conditions occurring in the ischemic/postischemic livers DAG apparently cannot bind to the enzyme and fulfill its function. Total phospholipids, phosphatidylcholine, and phosphatidylethanolamine, which significantly decrease at 60 min of ischemia, return to normal levels 1 hr after reperfusion.
Exp Mol Pathol 1992 Jun
PMID:State and activity of protein kinase C in postischemic reperfused liver. 163 81

We describe some properties on an Mr 30,000 thermolabile and trypsin-sensitive protein that activates phospholipase A2 (PLA2) and which was isolated from nervous tissue of the marine mollusk, Aplysia californica. A similar protein is present in rat cerebral cortex. This protein was partially purified from crude homogenates of nervous tissue by ion exchange chromatography on DEAE-Sephadex followed by size-exclusion high performance liquid chromatography (HPLC). It is loosely associated with membrane fractions, and is extracted by 0.05% Tween 20. Although similar in size to several previously described PLA2-stimulating proteins from non-neural mammalian cells and tissues, it differs from them in some aspects of biological activity. The protein promotes the release of eicosanoids from the membranes of intact Aplysia neurons prelabeled with [3H]arachidonic acid and appears to be an in vitro substrate for protein kinase C (PKC). PLA2-stimulating activity is greatly enhanced after exposing isolated ganglia to phorbol dibutyrate (PDBu) and is reduced by treatment with immobilized E. coli alkaline phosphatase. These observations suggest that phosphorylation of this stimulatory protein by PKC regulates PLA2 in neurons.
Brain Res Mol Brain Res 1991 Mar
PMID:A phospholipase A2-stimulating protein regulated by protein kinase C in Aplysia neurons. 164 37

Several lines of evidence now exist to suggest an interaction between the platelet-derived growth factor (PDGF) growth-stimulatory signal transduction pathway and the beta interferon (IFN-beta) growth-inhibitory signal transduction pathway. The most direct examples are inhibition of PDGF-mediated gene induction and mitogenesis by IFN-beta and the effects of activators and inhibitors of the IFN-inducible double-stranded RNA-dependent eIF2 kinase on expression of PDGF-inducible genes. To further investigate the nature of this PDGF/IFN-beta interaction, we selected BALB/c-3T3 cells for resistance to growth inhibition by IFN-beta and analyzed the phenotypes of resulting clonal lines (called IRB cells) with respect to PDGF signal transduction. Although selected only for IFN resistance, the IRB cells were found to be defective for induction of growth-related genes c-fos, c-myc and JE in response to PDGF. This block to signal transduction was not due to loss or inactivation of PDGF receptors, as immunoprecipitation of PDGF receptors with antiphosphotyrosine antibodies showed them to be present at equal levels in the BALB/c-3T3 and IRB cells and to be autophosphorylated normally in response to PDGF. Furthermore, treatment with other peptide growth factors (PDGF-AA, fibroblast growth factor, and epidermal growth factor) also failed to induce c-fos, c-myc, or JE expression in IRB cells. All of these growth factors, however, were able to induce another early growth-related gene, Egr-1. The block to signaling was not due to a defect in inositol phosphate metabolism, as PDGF treatment induced normal calcium mobilization and phosphotidylinositol-3-kinase activation in these cells. Activation of protein kinase C by phorbol esters did induce c-fos, c-myc, and JE in IRB cells, indicating that signalling pathways distal to this enzyme remained intact. We have previously shown that IFN-inducible enzyme activities, including double-stranded RNA-dependent eIF2 kinase and 2',5'-oligoadenylate synthetase, are normal in IRB cells. The finding that the induction of multiple growth-related genes by several independent growth factors is inhibited in these IFN-resistant cells suggests that there is a second messenger common to both growth factor and IFN signaling pathways and that this messenger is defective in these cells.
Mol Cell Biol 1991 Jun
PMID:BALB/c-3T3 fibroblasts resistant to growth inhibition by beta interferon exhibit aberrant platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor signal transduction. 164 46

The effects of synthetic [Asu1,7]eel calcitonin (CT) on the unidirectional inflow of Ca2+ were investigated in isolated rat liver cells by measuring the initial rate of 45Ca2+ uptake. CT increased Ca2+ inflow, with EC50 values (concentrations giving half-maximal effect) of 10(-10) M. The action of CT was in evidence within 15 s after the addition of 45Ca2+ to the cells. CT-activated Ca2+ inflow was completely blocked by the presence of the Ca2(+)-antagonist verapamil at a concentration of 10(-8) M. Meanwhile, epinephrine (10(-8) to 10(-4) M) or phenylephrine (10(-8) to 10(-4) M) increased Ca2+ inflow within 60 s after the addition of 45Ca2+ to the cells. Those hormonal effects were additively enhanced by the presence of CT (10(-8) M). Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, increased Ca2+ inflow at a concentration of 10(-9) to 10(-5) M. The presence of CT (10(-8) M) synergistically enhanced PMA-increased Ca2+ inflow at concentrations of 10(-7) to 10(-5) M. The present results suggest that CT can stimulate the rate of Ca2+ inflow in rat liver cells.
Mol Cell Endocrinol 1991 Jan
PMID:Stimulatory effect of calcitonin on Ca2+ inflow in isolated rat hepatocytes. 164 39

The whole-cell arrangement of the patch-clamp technique was used to examine the effect of protein kinase C (PKC) stimulation on ion channels in isolated guinea pig ventricular cells. In the presence of appropriate external solutions and drugs to reduce contamination from sodium, calcium, and potassium ion currents, application of phorbol 12-myristate 13-acetate or phorbol 12,13-dibutyrate, to stimulate PKC, activated a time-independent background current. The current-voltage relation for the PKC-activated current was linear over the voltage range of -90 to +60 mV. Alteration of the chloride equilibrium potential, brought about through changes in external and internal Cl- concentrations, shifted the reversal potential for the background current in a manner expected for a Cl- -selective ion channel. The PKC-activated current was reversibly inhibited by the S-(-)-enantiomer of the monocarboxylic acid derivative 8-chlorophenoxyproprionic acid, at a concentration that did not affect Ca2+ or delayed rectifier K+ currents. Dialysis of ventricular cells with partially purified PKC obtained from rat brain resulted in the activation of a large (greater than 1-nA) time-independent background current after addition of external phorbol 12,13-dibutyrate. In the presence of the beta-adrenergic receptor antagonist propranolol, norepinephrine activated a background current with properties similar to those of the PKC-sensitive current. It is concluded that cardiac ventricular cells contain PKC-activated Cl- channels, which may be regulated during alpha-adrenergic stimulation.
Mol Pharmacol 1991 Sep
PMID:Activation of a heart chloride current during stimulation of protein kinase C. 165 11

The present study characterizes the inhibitory effects of nodularin, a recently isolated hepatotoxic compound from the cyanobacterium Nodularia spumigena, on type 1 (PP1), type 2A, (PP2A), type 2B (PP2B), and type 2C (PP2C) protein phosphatases. Both PP2A and PP1 were potently inhibited (IC50 = 0.026 and 1.8 nM, respectively) by nodularin, whereas PP2B was inhibited to a lesser extent (IC50 = 8.7 microM). Nodularin had no apparent effect on PP2C, alkaline phosphatase, acid phosphatase, insulin receptor tyrosine kinase, protein kinase A, phosphorylase kinase, or protein kinase C. In a whole-cell extract of T51B liver cells, nodularin inhibited PP1 and PP2A activity with a potency similar to that seen with their purified catalytic subunits. Thus, due to the high specificity of nodularin for PP2A and PP1, this hepatotoxin may prove to be useful as a probe for distinguishing the activity of these protein phosphatases in cell extracts.
Mol Pharmacol 1991 Oct
PMID:Cyanobacterial nodularin is a potent inhibitor of type 1 and type 2A protein phosphatases. 165 93

The molecular mechanisms of cardiac myocyte growth are relevant to important problems in cardiovascular disease. A cell culture model has been developed to explore the role of adrenergic hormones in cardiac myocyte growth and gene expression. Activation of a cardiac myocyte alpha 1-adrenergic receptor by catecholamines induces hypertrophic growth of neonatal rat cardiac myocytes and initiates selective increases in contractile protein gene transcription. These effects on growth and gene expression do not depend on contractile activity. The cardiac myocytes contain at least two subtypes of alpha 1-adrenergic receptors and at least three isoforms of protein kinase C (PKC). A distinct alpha 1 receptor subtype may mediate hypertrophy and gene transcription. Different isoforms of PKC are translocated to different intracellular sites on activation, and there is evidence that the beta-PKC isoform may be an element in the signal transduction pathway from an alpha 1 receptor at the surface to the cardiac myocyte nucleus. Growth regulation through a beta-adrenergic receptor can also be demonstrated in the culture model. The growth response mediated through a beta-adrenergic receptor differs in several respects from that transduced through an alpha 1-adrenergic receptor.
Mol Cell Biochem
PMID:Adrenergic hormones and control of cardiac myocyte growth. 165 95

There is much evidence that G-proteins transduce the signal from receptors for Ca(2+)-mobilizing agonists to the phospholipase C that catalyzes the hydrolysis of phosphoinositides. However, the specific G-proteins involved have not been identified. We have recently purified a 42 kDa protein from liver that activates phosphoinositide phospholipase C and cross-reacts with antisera to a peptide common to G-protein alpha-subunits. It is proposed that this protein is the alpha-subunit of the G-protein that regulates the phospholipase in this tissue. Ca(2+)-mobilizing agonists and certain growth factors also promote the hydrolysis of phosphatidylcholine through the activation of phospholipases C and D in many cell types. This yields a larger amount of diacylglycerol for a longer time than does the hydrolysis of inositol phospholipids. Consequently phosphatidylcholine breakdown is probably a major factor in long-term regulation of protein kinase C. The functions of phosphatidic acid produced by phospholipase D are speculative, but there is evidence that it is a major source of diacylglycerol in many cell types. The regulation of phosphatidylcholine phospholipases is multiple and involves direct activation by G-proteins, and regulation by Ca2+, protein kinase C and perhaps growth factor receptor tyrosine kinases.
Mol Cell Biochem
PMID:Cell signalling through phospholipid breakdown. 165 98

Microsomes were prepared from cultured neonatal rat cardiomyocytes. Incubation of microsomes in buffer containing 5 microM CaCl2, 5 mM cholate and 100 nM [3H-]Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5) P2) resulted in the formation of [3H-]InsP3. GTP-gamma-S (125 microM) stimulated the production of [3H-]InsP3. Microsomes prepared from phorbol ester-treated (100 nM phorbol 12-myristate 13-acetate, PMA) cardiomyocytes showed decreased activities of basal as well as GTP-gamma-S-stimulated [3H-]PtdIns(4,5)P2 hydrolysis. In the microsomes a 15 kD protein was demonstrated to be the major substrate phosphorylated by intrinsic protein kinase C, which was activated by 0.5 mM Ca2+. Addition of phorbol ester (100 nM PMA) enhanced the 32P-incorporation into the 15 kD protein. Protein kinase C, purified from rat brain, in the presence of Ca2+, diglyceride, and phosphatidylserine did not change the phosphorylation pattern any further. In conclusion, it was shown that phorbol ester pretreatment of neonatal rat cardiomyocytes reduces microsomal GTP-gamma-S-stimulated PtdIns(4,5)P2-specific phospholipase C activity, as estimated with exogenous substrate, and that in cardiomyocyte microsomes phorbol ester activates protein kinase C-induced 15 kD protein phosphorylation. The results indicate that phorbol ester may down-regulate alpha 1-adrenoceptor mediated PtdIns(4,5)P2 hydrolysis by activation of protein kinase C-induced 15 kD protein phosphorylation.
Mol Cell Biochem 1991 Jun 26
PMID:Phorbol ester and the actions of phosphatidylinositol 4,5-bisphosphate specific phospholipase C and protein kinase C in microsomes prepared from cultured cardiomyocytes. 165 1


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