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)

In the human T-cell lymphoma line, HuT 78, proliferation and phorbol ester-induced growth arrest and differentiation were inhibited by the protein kinase C (PKC) inhibitor, staurosporine. By contrast, an alternative PKC inhibitor, H-7, inhibited proliferation but not phorbol ester-induced growth arrest. The cell line was found to contain both alpha and beta isoforms of PKC by Western blot techniques. A cell line, K-4, was cloned from HuT 78 in the presence of H-7 and this clone was found to be positive for PKC-alpha only. PKC-beta did not return on cultivation in the absence of H-7. Proliferation of K-4 was insensitive to inhibition with both H-7 and staurosporine. However, phorbol ester-induced growth arrest remained staurosporine sensitive. Phorbol-stimulated IL-2 secretion was minimal in the PKC-beta-deficient cell line. These data suggest that PKC-beta may be a regulatory enzyme for proliferation and stimulated interleukin-2 secretion in HuT 78 cells. Heterogeneity of responses to PKC activation may reflect the use of different isozymes in different intracellular pathways. The K-4 cell line should provide a useful tool in the dissection of involvement of PKC isozymes in cellular function.
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PMID:Development and characterization of a protein kinase C beta-isozyme-deficient T-cell line. 157 71

A bovine papilloma virus-derived vector was used to direct the high level expression in mouse C127 cells of three different cDNAs encoding the human interleukin-2 receptor. These were: the previously described cDNA clone isolated from the T-cell lymphoma, HUT-102; a cDNA clone isolated from mitogen-activated, normal peripheral blood T cells; and an altered version of the HUT-102 receptor in which Ser247, believed to be the site of protein kinase C-mediated phosphorylation, has been changed to an Ala residue. Fluorescence-activated cell-sorting using a monoclonal antibody directed against the human IL-2 receptor was used to derive stable lines of C127 cells expressing from 2-6 X 10(6) IL-2 binding sites per cell. However, all of these receptors bound IL-2 with low affinity.
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PMID:High level stable expression of human interleukin-2 receptors in mouse cells generates only low affinity interleukin-2 binding sites. 309 20

Using the T-cell lymphoma line HuT 78, and a clone derived from HuT 78, designated K-4, the role of protein kinase C (PKC) isozymes in the expression of a variety of T-cell surface antigens was investigated. HuT 78 expresses PKC isozymes alpha and beta while K-4 expresses only PKC alpha. Flow cytometric analysis revealed that incubation of HuT 78 cells with phorbol 12-myristate 13-acetate (PMA) results in significant down-regulation of surface expression of CD3. While K-4 cells expressed reduced amounts of CD3, a similar reduction in CD3 expression was not observed when these cells were stimulated with PMA. The regulation of expression of CD11a (LFA-1), CD44, CD45RA and CD45RO and of the class II molecules DR and DP in response to PMA, was similar in both cell lines.
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PMID:Regulation of CD3 expression in a protein kinase C isozyme-deficient T-cell line. 830 16

The acute retrovirus AKT8, isolated from an AKR mouse T-cell lymphoma, transforms mink lung cells in culture and is oncogenic when inoculated into newborn mice. The oncogene carried by this virus, v-akt, arose by recombination between Gag and the 5' untranslated region of the cellular gene c-akt. v-akt encodes a 105 kilodalton (kd) Gag-Akt fusion protein which is phosphorylated on serine and threonine residues. c-akt encodes a 55 kd serine-threonine protein-kinase, which is related to members of the protein kinase C (PKC) family and contains an SH2-like domain. The SH2-like and catalytic domains of Akt were expressed in E. coli as fusions to the carboxy-terminus of the Maltose binding protein (MBP). Antibodies against these proteins were raised in rabbits and they were used to determine the potential myristylation and subcellular localization of the v-akt and c-akt protein products. Immunoprecipitation of v-akt and c-akt from lysates of [35S]methionine and [3H]myristic acid labeled AKT8 transformed mink lung cells revealed that only v-akt was myristylated. Fractionation of Dounce-homogenized cellular extracts from uninfected and v-akt-transformed mink lung and PA317 cells and from uninfected PC12 cells by differential centrifugation showed that while the c-akt protein was localized primarily in the cytosol (90%), the v-akt protein was dispersed among the cellular compartments with approximately 40% on the plasma membranes, approximately 30% in the nucleus and approximately 30% in the cytosol. To determine whether the differences in post-translational modification and subcellular distribution between c-akt and v-akt translated into oncogenicity differences between the two proteins, we used retrovirus based constructs to express them both in the nontumorigenic rat T cell lymphoma line 5675. Intraperitoneal (IP) inoculation of the parental and c-akt expressing 5675 cells in nude Balb/c mice revealed that neither was oncogenic. In sharp contrast to these results, v-akt expressing 5675 cells inoculated in nude Balb/c mice were found to be highly oncogenic.
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PMID:The proteins encoded by c-akt and v-akt differ in post-translational modification, subcellular localization and oncogenic potential. 851 Sep 38

Protein kinase (PK)C theta is a critical regulator of mature T-cell activation and proliferation, being implicated in TCR-triggered nuclear factor (NF)-kappa B activation and providing important survival signals to leukemic T cells. We previously showed that overexpression of pT alpha/pre-TCR and constitutive activation of NF-kappa B characterize the T-cell leukemia/lymphoma developing in Notch3-IC transgenic mice. We report here that PKC theta is a downstream target of Notch3 signaling and that its activation and membrane translocation require a functional pre-TCR in order to trigger NF-kappa B activation in thymocytes and lymphoma cells of transgenic mice. Furthermore, deletion of PKC theta in Notch3-IC transgenic mice reduces the incidence of leukemia, correlating with decreased NF-kappa B activation. This paper therefore suggests that PKC theta mediates the activation of NF-kappa B by pre-TCR in immature thymocytes and contributes to the development of Notch3-dependent T-cell lymphoma.
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PMID:PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia. 1559 6

MCT-1 (multiple copies in T-cell lymphoma-1), a novel oncogene, was originally identified in T-cell lymphoma. A recent study has demonstrated that MCT-1 is highly expressed in 85% of diffuse large B-cell lymphomas (DLBCL). PKC (protein kinase C) plays an essential role in signal transduction for multiple biologically active substances for activating cellular functions and proliferation. In this study, we found that the mRNA and protein expression levels of MCT-1 were visibly decreased after knocking down PKC by siRNA in SUDHL-4 and OCI-LY8 DLBCL cell lines. A selective PKC inhibitor, sotrastaurin, effectively inhibited cell proliferation and induced cell apoptosis in a dose- and time-dependent manner. Meanwhile, we also observed that the cell cycle was arrested in the G1 phase in sotrastaurin-treated cells. In addition, MCT-1 was down-regulated in the sotrastaurin treatment group in vivo. Furthermore, we demonstrated that the PKC inhibitor sotrastaurin induced cell apoptosis and cell cycle arrest in DLBCL cells potentially through regulating the expression of MCT-1. Our data suggest that targeting PKC may be a potential therapeutic approach for lymphomas and related malignancies that exhibit high levels of MCT-1 protein.
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PMID:PKC inhibition of sotrastaurin has antitumor activity in diffuse large B-cell lymphoma via regulating the expression of MCT-1. 2953 46