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)

When 7721 human hepatocarcinoma cells were treated with 100 nM phorbol-12-myristate-13-acetate (PMA), the activity of N-acetylglucosaminyltransferase V(GnT-V) in the cells varied in accordance with the activity of membranous protein kinase C (PKC), but not with that of cytosolic PKC. Quercetin, a non-specific inhibitor of Ser/Thr protein kinase, and D-sphingosine and staurosporine, two specific inhibitors of PKC, blocked the activation of membranous PKC and GnT-V by PMA. Among the three inhibitors, quercetin was least effective. The inhibitory rates of quercetin and staurosporine toward membranous PKC and GnTV were proportional to the concentrations of the two inhibitors. The activities of GnTV and membranous protein kinase A (PKA) were also induced in parallel by dibutyryl cAMP (db-cAMP) and this induction was blocked by a specific PKA inhibitor. When cell free preparations of 7721 cells and human kidney were treated with alkaline phosphatase (ALP) to remove the phosphate groups, the GnTV activities were decreased. These results suggest that GnTV may be activated by membranous PKC or PKA, indirectly or directly, via phosphorylation of Ser/Thr residues.
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PMID:Regulation of N-acetylglucosaminyltransferase V by protein kinases. 874 53

The effects of the epidermal growth factor (EGF), a stimulator of tyrosine protein kinase (TPK), and phorblol-12-myristate-13-acetate (PMA), a stimulator of protein kinase C (PKC), on the activity of N-acetylglucosaminyltransferase V (GnT-V) were studied in human hepatocarcinoma cell line 7721 in order to elucidate the regulation of TPK and PKC on GnT-V. It was found that the GnT-V activity obviously increased after treatment of the cells with EGF or PMA for 48 h. A non-specific protein kinase inhibitor, quercetin, inhibited the activities of TPK and PKC(inhibited mainly the membranous TPK and PKC)as well as GnT-V simulatanously. Moreover, quercetin completely eliminated the stimulating effect of EGF or PMA on GnT-V. When Tyrohostin-25, a specific inhibitor of TPK, or sphingosine, the specific inhibitor of PKC, was used separately to substitute for quercetin, the induction effect of EGF of PMA on GnT-V was only partially eliminated. However, when both Tyrphostin-25 and sphingosine were added to the culture medium, the elevation of GnT-V caused by EGF or PMA was entirely blocked. Cycloheximide, a well-known inhibitor of protein synthesis, showed an effect similar to the inhibition of protein kinases;it not only inhibited the basal activity of GnT-V, but also abolished the inducing stimulation of GnT-V by EGF of PMA. These results indicate that EGF or PMA regulates the activity of GnT-V via protein kinases, and GnT-V is regulated by dual mechanism of membranous TPK and PKC. Membranous TPK is more important that membranous PKC in the regulation of GnT-V.
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PMID:Dual Regulation of Tyrosine Protein Kinase and Protein Kinase C on N-acetylglucosaminyltransferase V. 1216 8

An N-linked glycan often increased during oncogenic transformation contains beta(1,6)-linked GlcNAc, synthesized by the N-acetylglucosaminyltransferase V (GnT-V). The progression of polyoma middle T-antigen oncoprotein-induced mammary carcinomas in GnT-V null mice was significantly retarded compared with that observed in wild-type mice. The matrix adhesion of mouse embryonic fibroblasts (MEF) from GnT-V null and wild-type mice was investigated to understand the mechanism by which deletion of GnT-V could retard tumor progression. GnT-V null MEF displayed enhanced adhesion to and spreading on fibronectin-coated plates with concomitant inhibition of cell migration. GnT-V null MEF also showed increased focal adhesion kinase tyrosine phosphorylation, consistent with decreased cell motility on fibronectin-coated plates. Expression of GnT-V cDNA in the null MEF reversed these abnormal characteristics, indicating the direct involvement of N-glycosylation events in these phenotypic changes. The alpha5beta1 fibronectin receptors exhibited increased clustering on the null MEF cell surfaces, consistent with previous studies that observed less integrin clustering in cells overexpressing GnT-V. Most surprisingly, GnT-V null MEF displayed increased expression levels of both alpha5 and beta1 subunits in lysates and on the cell surface. Increased alpha5beta1 expression in the null MEF was because of increased alpha5beta1 transcript levels that declined after re-expression of GnT-V cDNA, confirming that increased alpha5beta1 expression in null MEF was because of changes in GnT-V expression. The increased null MEF transcripts were shown to be caused at least in part by increased integrin promoter activity. Moreover, increased alpha5beta1 integrin transcripts in GnT-V null MEF were not due to a differential response to fibronectin; rather, they appeared to be mediated by activation of a protein kinase C signaling pathway. These results demonstrate that deletion of MEF GnT-V resulted in enhanced integrin clustering and activation of alpha5beta1 transcription by protein kinase C signaling, which in turn up-regulated levels of cell surface alpha5beta1 fibronectin receptors that resulted in increased matrix adhesion and inhibition of migration.
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PMID:Deletion of mouse embryo fibroblast N-acetylglucosaminyltransferase V stimulates alpha5beta1 integrin expression mediated by the protein kinase C signaling pathway. 1561 21