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)

The Drosophila melanogaster cell line mbn-2 was explored as a model system to study insect immune responses in vitro. This cell line is of blood cell origin, derived from larval hemocytes of the mutant lethal (2) malignant blood neoplasm (1(2)mbn). The mbn-2 cells respond to microbial substances by the activation of cecropin genes, coding for bactericidal peptides. The response is stronger than that previously described for SL2 cells, and four other tested Drosophila cell lines were totally unresponsive. Bacterial lipopolysaccharide, algal laminarin (a beta-1,3-glucan), and bacterial flagellin were strong inducers, bacterial peptidoglycan fragments gave a weaker response, whereas a formyl-methionine-containing peptide had no effect. Experiments with different drugs indicate that the response may be mediated by a G protein, but not by protein kinase C or eicosanoids, and that it requires a protein factor with a high rate of turnover.
 ...
PMID:In vitro induction of cecropin genes--an immune response in a Drosophila blood cell line. 144 51

Binding of zymosan particles to macrophage beta-glucan receptors has previously been shown to trigger exocytosis of preformed lysosomal contents. In the present study, the involvement of Ca(2+)-, PKC-, and pH-dependent processes in the signaling to macrophage lysosomal secretion by zymosan was investigated. Also, the PKC dependence of lysosomal secretion in response to some soluble agents that directly alters intracellular pH was considered. Signaling to macrophage lysosomal secretion differs from that of many other secretory systems, because an elevation of cytosolic Ca2+ did not trigger a large secretory response, nor did attempts to reduce cytosolic Ca2+ affect the lysosomal secretory response to other stimuli. PKC activation by phorbol diester was also a poor stimulus of lysosomal secretion. However, when triggered by zymosan or by soluble stimuli raising lysosomal pH, the secretory response could be down-regulated by a prior prolonged incubation with phorbol diester. Such treatment also had marked effects on the binding and uptake of zymosan particles, the study of which was made possible by a novel approach. Furthermore, a synergistic effect on lysosomal secretion was obtained when stimuli that elevated lysosomal pH and stimuli that activated PKC were combined. This is of likely relevance for the secretory response to zymosan particles, a stimulus that both activates PKC and elevates lysosomal pH. The secretory response to zymosan was furthermore shown to be inhibited by a reduction of extracellular pH or [Na+], conditions that impair macrophage extrusion of acid equivalents. Earlier studies using soluble stimuli have shown a sensitivity of the secretory response to changes in cytosolic pH. We suggest a model in which the lysosomal secretory response to an elevation of lysosomal pH (1) is dependent on basal PKC activity and (2) can be enhanced further by activation of PKC. We consider PKC activity and elevation of lysosomal pH as independent and necessary signals, while cytosolic pH has a modulatory effect on some component(s) in the signal transduction pathway or in the secretory apparatus itself.
 ...
PMID:Protein kinase C and intracellular pH regulate zymosan-induced lysosomal enzyme secretion in macrophages. 756 26

The PKC1 gene of the budding yeast Saccharomyces cerevisiae encodes a homolog of the alpha, beta, and gamma isoforms of mammalian PKC that is essential for cell growth. Loss of PKC1 function results in a cell lysis defect that is suppressed by osmotic stabilizing agents, suggesting a defect in cell wall integrity. In this study, we show that Pkc1p-depleted cells develop holes in their cell walls positioned at their bud tips, the site to which growth is focused during polarized cell growth. This result suggests that pkc1 mutants are deficient in the process of cell wall remodeling during growth. In further support of this model, cells bearing a pkc1 delta mutation, allowed to proliferate in the presence of osmotic stabilizing agents, possessed cell walls that were only 60% as thick as wild-type cell walls. This diminution in cell wall material affected both the beta-glucan layer and the mannoprotein layer. We have exploited the cell lysis defect of pkc1 mutants to identify genes that function within the same signalling pathway at points downstream of PKC1. These genes comprise a protein kinase cascade that culminates in the activation of the MAP kinase homolog Mpk1p. The proposed order of protein kinase function, based on genetic experiments, is Pkc1p to Bck1p to Mkk1/2p to Mpk1p. Consistent with the proposed model, Pkc1p selectively phosphorylates Bck1p in vitro and Mpk1p protein kinase activity requires a functional BCK1 gene.
 ...
PMID:Dissecting the protein kinase C/MAP kinase signalling pathway of Saccharomyces cerevisiae. 787

A characterization of the S. cerevisiae KRE6 and SKN1 gene products extends previous genetic studies on their role in (1-->6)-beta-glucan biosynthesis (Roemer, T., and H. Bussey. 1991. Yeast beta-glucan synthesis: KRE6 encodes a predicted type II membrane protein required for glucan synthesis in vivo and for glucan synthase activity in vitro. Proc. Natl. Acad. Sci. USA. 88:11295-11299; Roemer, T., S. Delaney, and H. Bussey. 1993. SKN1 and KRE6 define a pair of functional homologs encoding putative membrane proteins involved in beta-glucan synthesis. Mol. Cell. Biol. 13:4039-4048). KRE6 and SKN1 are predicted to encode homologous proteins that participate in assembly of the cell wall polymer (1-->6)-beta-glucan. KRE6 and SKN1 encode phosphorylated integral-membrane glycoproteins, with Kre6p likely localized within a Golgi subcompartment. Deletion of both these genes is shown to result in a dramatic disorganization of cell wall ultrastructure. Consistent with their direct role in the assembly of this polymer, both Kre6p and Skn1p possess COOH-terminal domains with significant sequence similarity to two recently identified glucan-binding proteins. Deletion of the yeast protein kinase C homolog, PKC1, leads to a lysis defect (Levin, D. E., and E. Bartlett-Heubusch. 1992. Mutants in the S. cerevisiae PKC1 gene display a cell cycle-specific osmotic stability defect. J. Cell Biol. 116:1221-1229). Kre6p when even mildly overproduced, can suppress this pkc1 lysis defect. When mutated, several KRE pathway genes and members of the PKC1-mediated MAP kinase pathway have synthetic lethal interactions as double mutants. These suppression and synthetic lethal interactions, as well as reduced beta-glucan and mannan levels in the pkc1 null wall, support a role for the PKC1 pathway functioning in cell wall assembly. PKC1 potentially participates in cell wall assembly by regulating the synthesis of cell wall components, including (1-->6)-beta-glucan.
 ...
PMID:Characterization of the yeast (1-->6)-beta-glucan biosynthetic components, Kre6p and Skn1p, and genetic interactions between the PKC1 pathway and extracellular matrix assembly. 792 94

Previously we have shown that reactive oxygen species (ROS) formation induced by phorbol ester in association with vanadate is essential for protein tyrosine phosphorylation and phospholipase A2 (PLA2) activation. Here we show that the interaction of beta-glucan particles (glucanp) or zymosan with complement receptor type 3 (CR3) leads, when associated with vanadate, to a cascade of reactions culminating in PLA2 activation. Vanadate + zymosan (or glucanp) markedly enhance protein tyrosine phosphorylation in bone marrow derived macrophages (BMMs), whereas neither of the agents alone has any effect. The enhancement was due to both sustained activation of protein tyrosine kinase (PTK) and inactivation of protein tyrosine phosphatase (PTP) as assessed in lysates of treated cells. Zymosan elevates membranal PKC, an effect that is potentiated by vanadate. Activation of both PTK and PKC leads to the activation of NADPH oxidase and to ROS formation. The formed ROS together with vanadate are potent inactivators of PTP leading to amplification of tyrosine phosphorylation and myelin basic protein kinase (MBP-K) activation. The activation of the cascade of protein kinases eventually leads to activation of PLA2. All the activation steps, i.e., activation of PTK, NADPH oxidase, MBP-K,PLA2 and the inactivation of PTP are sensitive to the NADPH oxidase inhibitor diphenyleneiodonium (DPI), to antioxidants and to PKC inhibitors. Thus, ROS formation (in the presence of vanadate) is critical for protein phosphorylation processes constituting the regulatory pathway of PLA2 activation by ligand-CR3 interaction.
 ...
PMID:A role for reactive oxygen species in zymosan and beta-glucan induced protein tyrosine phosphorylation and phospholipase A2 activation in murine macrophages. 803 63

To obtain more information about the cell wall organization of Saccharomyces cerevisiae, we have developed a novel screening system to obtain cell wall-defective mutants, using a density gradient centrifugation method. Nine hypo-osmolarity-sensitive mutants were classified into two complementation groups, hpo1 and hpo2. Phase contrast microscopic observation showed that mutant cells bearing lesions at either locus became abnormally large. A gene that complemented the mutant phenotype of hpo2 was cloned and sequenced. This gene turned out to be identical to PKC1, which encodes the yeast homologue of mammalian protein kinase C. Complementation tests with pkc1 delta showed that hpo2 is allelic to pkc1. To study the reason for the fragility of hpo2 cells, cell wall was isolated and the glucan was analyzed. The amount of alkali, acid-insoluble glucan, which is responsible for the rigidity of the cell wall, was reduced to about 30% that of the wild-type cell and this may be the major cause of the fragility of the hpo2 mutant cell. Analysis of total wall proteins in hpo2 mutant cells on SDS-polyacrylamide gels revealed that a 33 kDa protein was overproduced two- to threefold relative to the wild-type level. This 33 kDa protein was identified as a beta-glucanase, encoded by BGL2. Disruption of BGL2 in the hpo2 mutant partially rescued the growth rate defect. This suggests that the PKC1 kinase cascade regulates BGL2 expression negatively and overproduction of the beta-glucanase is partially responsible for the growth defect.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The hypo-osmolarity-sensitive phenotype of the Saccharomyces cerevisiae hpo2 mutant is due to a mutation in PKC1, which regulates expression of beta-glucanase. 815 14

We have previously presented indirect in vivo evidence for the involvement of islet acid glucan-1,4-alpha-glucosidase (acid amyloglucosidase), a lysosomal glucose-producing enzyme, in certain insulin secretory processes. In the present in vitro and in vivo investigation, we studied whether differential changes in islet acid amyloglucosidase activity would be related to the insulin secretory response induced by two mechanistically different secretagogues, the sulphonylurea derivative, glibenclamide and the acetylcholine receptor agonist, carbachol. It was observed that the selective alpha-glucosidehydrolase inhibitors emiglitate and acarbose markedly reduced glibenclamide-induced insulin release from isolated islets. Insulin release stimulated by carbachol or the protein kinase C activator TPA (12-O-tetradecanoylphorbol 13-acetate), was not inhibited. Basal insulin secretion was unaffected by emiglitate and acarbose. Further, pretreatment of mice with emiglitate resulted in a marked reduction of the in vivo insulin response to glibenclamide. Moreover, in vivo pretreatment with purified fungal amyloglucosidase ('enzyme replacement'), a procedure known to increase islet amyloglucosidase activity, greatly enhanced the insulin response to i.v. glibenclamide. This insulin release was accompanied by a marked depression of the blood glucose levels. In contrast, enzyme pretreatment did not influence the insulin response or the blood glucose levels after carbachol. The data strongly suggest that islet acid amyloglucosidase is involved in the insulin secretory processes induced by glibenclamide but not in those involving stimulation of muscarinic receptors or direct activation of protein kinase C. The results also indicate separate or at least partially separate pathways for insulin release induced by glibenclamide and cholinergic stimulation.
 ...
PMID:Changes in islet glucan-1,4-alpha-glucosidase activity modulate sulphonylurea-induced but not cholinergic insulin secretion. 827 68

Degranulation (regulated exocytosis) of crayfish granular blood cells and release of the prophenoloxidase activating system can be triggered by two endogenous ligands, a 76-kDa cell adhesion protein or a beta-1,3-glucan-binding protein when reacted with beta-1,3-glucan (beta GBP-L). These ligands bind a recently described membrane receptor. Degranulation triggered by these ligands was inhibited by the protein kinase C (pkC) inhibitor staurosporine or by the tyrosine kinase inhibitor herbimycin A. Incubation with the 76-kDa protein increased tyrosine phosphorylation of a granular cell protein of approximately 80 kDa. In addition, the pkC activating phorbol esters PMA or beta PDD degranulated the cells in a dose-dependent manner, whereas the control isomeric phorbol ester alpha PDD that does not activate pkC did not have any effect on the cells. Thus, we propose that binding of the 76-kDa protein or beta GBP-L to the receptor triggers cellular responses via a pathway that includes pkC activation and protein tyrosine phosphorylation.
 ...
PMID:Intracellular signaling in arthropod blood cells: involvement of protein kinase C and protein tyrosine phosphorylation in the response to the 76-kDa protein or the beta-1,3-glucan-binding protein in crayfish. 829 48

In fission yeast protein kinase C homologues (Pck1 and Pck2) are essential for cell morphogenesis. We have isolated mok1(+) in a genetic screen to identify downstream effectors for Pck1/2. mok1(+) is essential for viability and encodes a protein that has several membrane-spanning domains and regions homologous to glucan metabolic enzymes. mok1 mutant shows abnormal cell shape, randomization of F-actin and weak cell wall. Biochemical analysis shows that Mok1 appears to have alpha-glucan synthase activity. Mok1 localization undergoes dramatic alteration during the cell cycle. It localizes to the growing tips in interphase, the medial ring upon mitosis, a double ring before and dense dot during cytokinesis. Double immunofluorescence staining shows that Mok1 exists in close proximity to actin. The subcellular localization of Mok1 is dependent upon the integrity of the F-actin cytoskeleton. Conversely, overexpression of mok1(+) blocks the translocation of cortical actin from one end of the cell to the other. pck2 mutant is synthetically lethal with mok1 mutant, delocalizes Mok1 and shows a lower level of alpha-glucan. These results indicate that Mok1 plays a crucial role in cell morphogenesis interdependently of the actin cytoskeleton and works as one of downstream effectors for Pck1/2.
 ...
PMID:Fission yeast alpha-glucan synthase Mok1 requires the actin cytoskeleton to localize the sites of growth and plays an essential role in cell morphogenesis downstream of protein kinase C function. 1008 62

Previous work showed that the GTP-binding protein Rho1p is required in the yeast, Saccharomyces cerevisiae, for activation of protein kinase C (Pkc1p) and for activity and regulation of beta(1-->3)glucan synthase. Here we demonstrate a hitherto unknown function of Rho1p required for cell cycle progression and cell polarization. Cells of mutant rho1(E45I) in the G1 stage of the cell cycle did not bud at 37 degrees C. In those cells actin reorganization and recruitment to the presumptive budding site did not take place at the nonpermissive temperature. Two mutants in adjacent amino acids, rho1(V43T) and rho1(F44Y), showed a similar behavior, although some budding and actin polarization occurred at the nonpermissive temperature. This was also the case for rho1(E45I) when placed in a different genetic background. Cdc42p and Spa2p, two proteins that normally also move to the bud site in a process independent from actin organization, failed to localize properly in rho1(E45I). Nuclear division did not occur in the mutant at 37 degrees C, although replication of DNA proceeded slowly. The rho1 mutants were also defective in the formation of mating projections and in congregation of actin at the projections in the presence of mating pheromone. The in vitro activity of beta(1-->3)glucan synthase in rho1 (E45I), although diminished at 37 degrees C, appeared sufficient for normal in vivo function and the budding defect was not suppressed by expression of a constitutively active allele of PKC1. Reciprocally, when Pkc1p function was eliminated by the use of a temperature-sensitive mutation and beta(1-->3)glucan synthesis abolished by an echinocandin-like inhibitor, a strain carrying a wild-type RHO1 allele was able to produce incipient buds. Taken together, these results reveal a novel function of Rho1p that must be executed in order for the yeast cell to polarize.
 ...
PMID:The GTP-binding protein Rho1p is required for cell cycle progression and polarization of the yeast cell. 1042 91


1 2 3 4 5 Next >>