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)

An analysis of the nucleoprotein (NP) of 29 different influenza A viruses by phosphopeptide fingerprinting revealed three prototype patterns. The first, which was a complex pattern consisting of six to seven phosphopeptides, another which was relatively simple consisted of two or three phosphopeptides, and a third one which was complex but was missing the main phosphopeptide shared by the two other patterns. Phosphoserine was the only labelled phosphamino acid detected. A tentative deduction of two of the phosphate attachment sites (serine residues at positions 3 and 473) could be made by comparison of the known amino acid sequences of the NPs of 25 strains. No correlation was found between species specificity or subtype or year of isolation of the strains. During the infectious cycle the fingerprint underwent significant changes, indicating subtle phosphorylation and dephosphorylation of the NP at various stages during viral multiplication. Most of the phosphopeptides were metabolically stable; however one major phosphopeptide, which was not found in the NP of mature virions, exhibited a high turnover (presumably serine at position 3). The phosphopeptide fingerprint could be significantly influenced in vivo by the specific stimulation of cellular protein kinase C by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate or by its inhibition with the isoquinoline sulphonamide H7.H7 specifically inhibited the replication of influenza A viruses by deregulation of viral protein synthesis without interfering with the multiplication of a parainfluenza virus (Newcastle disease virus), an alphavirus (Semliki Forest virus) or a flavivirus (West Nile). Therefore the correct phosphorylation of the NP of influenza viruses appears to be essential for influenza virus replication.
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PMID:Differential phosphorylation of the nucleoprotein of influenza A viruses. 277 38

Addition of tumor-promoting phorbol diesters to [32P]phosphate-labeled A431 human epidermoid carcinoma cells caused an increase in the phosphorylation state of the transferrin receptor. The A431 cell transferrin receptor was also found to be a substrate for protein kinase C in vitro. Tryptic phosphopeptide mapping of the transferrin receptor resolved the same two phosphopeptides (X and Y) after either protein kinase C phosphorylation in vitro or treatment of labeled A431 cells with phorbol diesters. [32P]Phosphoserine was the only labeled phosphoamino acid detected. Phosphopeptide X was shown to be an incomplete tryptic digestion product which could be further digested with trypsin to generate the limit tryptic phosphopeptide (Y). Radiosequence analysis of [32P]phosphopeptide Y demonstrated that the [32P]phosphoserine was the second residue from amino terminus of the peptide. This receptor phosphopeptide was found to co-migrate with the synthetic peptide Phe-Ser(P)-Leu-Ala-Arg (where Ser(P) is phosphoserine) during reverse-phase high pressure liquid chromatography and two-dimensional thin layer electrophoresis and chromatography. The peptide Phe-Ser(P)-Leu-Ala-Arg is an expected tryptic fragment of the cytoplasmic domain of the transferrin receptor corresponding to residues 23-27. We conclude that the major site of protein kinase C phosphorylation of the transferrin receptor in vivo and in vitro is serine 24. This phosphorylation site is located within the intracellular domain of the transferrin receptor, 38 residues away from the predicted transmembrane domain.
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PMID:Identification of serine 24 as the unique site on the transferrin receptor phosphorylated by protein kinase C. 301 73

The epidermal growth factor (EGF) receptor is regulated by EGF-stimulated autophosphorylation and by phorbol ester-stimulated, protein kinase C (Ca2+/phospholipid-dependent enzyme) mediated phosphorylation at identified sites. The EGF receptor contains additional phosphorylation sites including a prominent phosphothreonine and several phosphoserines which account for the majority of phosphate covalently bound to the receptor in vivo. We have identified three of these sites in EGF receptor purified from 32P-labeled A431 cells. The major phosphothreonine was identified as threonine 669 in the EGF receptor sequence. Phosphoserine residues were identified as serines 671 and 1046/1047 of the EGF receptor. Two other phosphoserine residues were localized to tryptic peptides containing multiple serine residues located carboxyl-terminal to the conserved protein kinase domain. The amino acid sequences surrounding the three identified phosphorylation sites are highly conserved in the EGF receptor and the protein products of the v-erb B and neu oncogenes. Analysis of predicted secondary structure of the EGF receptor reveals that all of the phosphorylation sites are located near beta turns. In A431 cells phosphorylation of the serine residues was dependent upon serum. In mouse B82 L cells transfected with a wild type human EGF receptor. EGF increased the 32P content in all tryptic phosphopeptides. A mutant EGF receptor lacking protein tyrosine kinase activity was phosphorylated only at threonine 669. Regulated phosphorylation of the EGF receptor at these threonine and serine residues may influence aspects of receptor function.
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PMID:Epidermal growth factor receptor threonine and serine residues phosphorylated in vivo. 313 33

Deoxycytidine (dCyd) kinase was effectively phosphorylated by protein kinase C. The reaction was rapid, occurring at 4 degrees C as well as at 37 degrees C and approximately 0.7 mol of phosphate could be incorporated per mol of deoxycytidine kinase. Phosphoserine was the primary amino acid to be phosphorylated. Phosphorylation of deoxycytidine kinase resulted in a 100% increase in the Vmax using dCyd as a substrate (52.16 +/- 1.3 versus 104.47 +/- 11.4 nmol/min/mg protein), and an increase in the apparent Km (2.0 +/- 0.2 microM versus 6.9 +/- 1.2 microM). The inactive antimetabolite, ara-C, is activated within a cell by deoxycytidine kinase phosphorylation of the prodrug. Recent studies have shown that ara-C activates protein kinase C in vivo [1]. Furthermore, ara-C has been shown to be metabolized to ara-CDP-choline via reversal of the cholinephosphotransferase [2] producing diglyceride, a cellular activator of protein kinase C. Thus, in situ, deoxycytidine kinase may be phosphorylated by protein kinase C with the result that self-potentiation of ara-C toxicity may occur via increased activity of deoxycytidine kinase.
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PMID:Deoxycytidine kinase is phosphorylated in vitro by protein kinase C alpha. 798 Dec 28

Phosphorylation of keratin intermediate filaments (IF) is known to affect their assembly state and organization; however, little is known about the mechanisms regulating keratin phosphorylation. In this study, we demonstrate that shear stress, but not stretch, causes disassembly of keratin IF in lung alveolar epithelial cells (AEC) and that this disassembly is regulated by protein kinase C delta-mediated phosphorylation of keratin 8 (K8) Ser-73. Specifically, in AEC subjected to shear stress, keratin IF are disassembled, as reflected by their increased solubility. In contrast, AEC subjected to stretch showed no changes in the state of assembly of IF. Pretreatment with the protein kinase C (PKC) inhibitor, bisindolymaleimide, prevents the increase in solubility of either K8 or its assembly partner K18 in shear-stressed AEC. Phosphoserine-specific antibodies demonstrate that K8 Ser-73 is phosphorylated in a time-dependent manner in shear-stressed AEC. Furthermore, we showed that shear stress activates PKC delta and that the PKC delta peptide antagonist, delta V1-1, significantly attenuates the shear stress-induced increase in keratin phosphorylation and solubility. These data suggested that shear stress mediates the phosphorylation of serine residues in K8, leading to the disassembly of IF in alveolar epithelial cells. Importantly, these data provided clues regarding a molecular link between mechanically induced signal transduction and alterations in cytoskeletal IF.
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PMID:Keratin 8 phosphorylation by protein kinase C delta regulates shear stress-mediated disassembly of keratin intermediate filaments in alveolar epithelial cells. 1597 20