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

Thymus myosin, light chains and a synthetic peptide (S-S-K-R-A-K-A-K-T-T-K-K-R-P-Q-R-A-T-S-N-V-F-S) corresponding to the N-terminal sequence of smooth muscle myosin light chains were compared as substrates for calcium/calmodulin-dependent protein kinase (MLCK), calcium/phospholipid-dependent protein kinase (PKC), and a MgATP-activated protein kinase (H4PK) from lymphoid cells. All protein kinases catalyzed phosphorylation of the substrates although H4PK showed higher affinity for isolated light chains and the peptide. Phosphoamino acid analysis and analysis of thermolysin peptides established that PKC catalyzed phosphorylation of threonine-9 or 10. In addition, PKC and H4PK catalyzed phosphorylation at serine-19, the MLCK site. Collectively the data support the hypothesis that myosin filament assembly in nonmuscle cells may be regulated by a variety of calcium-dependent and calcium-independent protein kinases.
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PMID:Nonmuscle myosin phosphorylation sites for calcium-dependent and calcium-independent protein kinases. 308 Sep 87

Since TCR/CD3 modulation may be involved in induction of T cell tolerance to self antigens, we compared ligand-induced TCR/CD3 internalization by a CTL clone and by immature thymocytes and mature T cells from mice bearing the same TCR alpha beta as transgene. The ligand used is a monoclonal antibody (mAb) specific for the receptor expressed by the clone and transgenic mice (anti-Ti mAb). CD8+ splenocytes triggered by anti-Ti mAb internalize the ligand-TCR/CD3 complex at a low rate, through a mechanism inhibited by the protein tyrosine kinase (PTK) inhibitor genistein and by staurosporine, a potent but non selective protein kinase C (PKC) inhibitor. This pattern of inhibition was similar to that observed in the CTL clone. Anti-Ti mAb induced TCR/CD3 internalization in CD4+CD8+ thymocytes at a high rate, through a mechanism which was insensitive to either genistein or staurosporine. In the CTL clone, genistein was shown to inhibit TCR/CD3 surface redistribution preceeding internalization. To characterize the PTK possibly involved in this step, we analyzed TCR/CD3 associated kinases in mature T splenocytes and thymocytes. Kinase activities present in anti-Ti mAb immunoprecipitates phosphorylated the CD3 components gamma, delta, epsilon, and zeta in both cell types although the intensity was stronger in splenic than in thymocyte extracts, whereas the phosphorylation of 70, 14 and 12kD substrates was more pronounced in thymocytes than in splenocytes. Comparable amounts of CD3 components were coprecipitated with and phosphorylated by p56lck and p59fyn respectively, in both cell types.
Thymus 1994
PMID:Developmental control of T-cell receptor internalization. 786 44

Major developmental transitions in thymocyte differentiation are accompanied by sharp alterations in cAMP metabolism. We have analyzed the cAMP accumulation responses of cell populations representing successive stages of T-cell development, namely: immature TcR- thymocytes from SCID mice, proliferating cortical blasts, small cortical thymocytes, medullary thymocytes and peripheral T cells. We find that all classes of thymocytes exhibit higher cAMP synthesis in response to forskolin than peripheral T cells. In immature TcR- thymocytes, this high capacity is buffered by efficient phosphodiesterase activity, but in CD4+CD8+TcRlow thymocytes, phosphodiesterase activity becomes much less effective. Phosphodiesterase activity then rises again after positive selection. The ability of thymocytes to respond to prostaglandin E is regulated distinctly from their ability to respond to forskolin. Unlike forskolin, PGE1 induces cAMP synthesis to similar levels in all classes of thymocytes, possibly due to partial activation of phosphodiesterase in cortical thymocytes by PGE1. Finally, we report a novel effect of Ca2+/protein kinase C signaling on cAMP accumulation, which occurs selectively in the proliferating cortical blasts.
Thymus
PMID:Developmental regulation of cAMP signaling pathways in thymocyte development. 852 7

13 murine tissues and 12 cell lines were tested for the expression of the novel protein kinase C (PKC) isoenzyme mu. Using two different PKC mu antibodies (sc-639 and P26720), PKC mu was detected in all tissues and cells and thus proved to be an ubiquitous PKC isotype. However, in some tissues, PKC mu was recognized only by the antibody P26720 and not by sc-639. Thymus, lung and peripheral blood mononuclear cells expressed the greatest amount of PKC mu. Recognition of PKC mu by the antibody sc-639 was drastically impaired when treating keratinocytes or mouse skin in vivo with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), thus mimicking down-regulation of PKC mu. The lack of a decrease in the PKC mu amount and, thus, the lack of down-regulation could be proved using the antibody P26720. This antibody was able to recognize PKC mu in extracts of untreated as well as TPA-treated tissues or cells. Phosphorylation of proteins in a cell-free system (cell or tissue extracts) in the presence and absence of TPA or other PKC activators and various protein kinase inhibitors indicated that phosphorylation of activated PKC mu caused its reduced interaction with the antibody sc-639. Therefore, this antibody might present a well suited tool for the detection of activated PKC mu in vivo. Moreover, our results clearly show that some antibodies, such as sc-639, might be able to selectively detect non-phosphorylated or phosphorylated forms of a protein, and that such properties of an antibody have to be studied carefully before the latter can be used for reliable quantitative determination of this protein. We consider this information important to avoid misinterpretation of data concerning the immunological quantification of proteins such as PKC mu.
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PMID:Immunological demonstration of protein kinase C mu in murine tissues and various cell lines. Differential recognition of phosphorylated forms and lack of down-regulation upon 12-O-tetradecanoylphorphol-13-acetate treatment of cells. 897 62

The induction of cytochrome P450 1A1 (CYP1A1) is one of the most sensitive responses associated with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. The mechanisms that underlie this response are not completely understood, particularly in lymphoid tissues that may be used in biomarker studies in humans. CYP1A1 mRNA expression and enzyme activity (ethoxyresorufin-o-deethylase, EROD) were investigated in rat thymus and spleen and isolated thymocytes and splenocytes in culture. Thymus- or spleen-derived microsomes from rats treated in vivo with TCDD showed induced EROD activity after as little as 12 h following a single exposure to TCDD (5 microg/kg body weight). Resting rat thymocytes in culture had detectable levels of EROD activity and CYP1A1 mRNA expression which increased following in vitro exposure to > or = 0.1 nM TCDD for 24 or 48 h. Interestingly, concomitant in vitro exposure of rat thymocytes to TCDD and the mitogen concanavalin A (Con A) inhibited the induction of EROD activity, which is in contrast to the response of cultured human peripheral blood lymphocytes (Landi et al., 1994; Pharmacogenetics 4, 242 246). Resting rat splenocytes in culture had no detectable EROD activity and CYP1A1 activity could not be induced by in vitro TCDD exposure, in the presence or absence of Con A. These results suggest that the relative maturation state of the cells is important in regulating the expression of CYP1A1, since splenocytes represent a more mature population of B and T lymphocytes. TCDD-induced CYP1A1 expression in cultured rat thymocytes was inhibited by the addition of calphostin C, a specific protein kinase C (PKC) inhibitor, suggesting a role for PKC as a second messenger in the CYP1A1 induction pathway. In vivo co-exposure with phorbol-myristate-acetate (PMA) and TCDD also inhibited CYP1A1 induction. Again, suggesting a role for PKC in CYP1A1 induction. Together, these results indicate that relative lymphocyte maturation state and the PKC pathway are important factors in regulating the expression of CYP1A1.
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PMID:Cytochrome P450 1A1 induction in rat lymphoid tissues following in vivo and in vitro exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin requires protein kinase C. 939 54