PKCθ is required for the activation of human T lymphocytes induced by CD43 engagement
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The turnover of phosphoinositides leading to PKC activation constitutes one of the principal axes of intracellular signaling. In T lymphocytes, the enhanced and prolonged PKC activation resulting from the engagement of the TcR and co-receptor molecules ensures a productive T cell response. The CD43 co-receptor promotes activation and proliferation, by inducing IL-2 secretion and CD69 expression. CD43 engagement has been shown to promote phosphoinositide turnover and DAG production. Moreover, PKC activation was found to be required for the activation of the MAP kinase pathway in response to CD43 ligation. Here we show that CD43 engagement led to the membrane translocation and enzymatic activity of specific PKC isoenzymes: cPKC (α/β), nPKC (ε and θ), aPKC (ζ) and PKCμ. We also show that activation of PKCθ resulting from CD43 ligation induced CD69 expression through an ERK-dependent pathway leading to AP-1, NF-κB activation and an ERK independent pathway promoting NFAT activation. Together, these data suggest that PKCθ plays a critical role in the co-stimulatory functions of CD43 in human T cells. © 2004 Elsevier Inc. All rights reserved.
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AP-1; CD43; CD69; NF-κB; NFAT; PKC; T cell activation apolipoprotein A1; CD69 antigen; immunoglobulin enhancer binding protein; interleukin 2; leukosialin; mitogen activated protein kinase; phosphatidylinositide; protein kinase C; transcription factor NFAT; CD69 antigen; DNA; DNA binding protein; immunoglobulin enhancer binding protein; isoenzyme; leukocyte antigen; leukosialin; nuclear protein; PRKCQ protein, human; protein kinase C; sialoglycoprotein; SPN protein, human; T lymphocyte antigen; transcription factor; transcription factor AP 1; transcription factor NFAT; article; cell activation; cell proliferation; controlled study; cytokine release; enzyme activity; gene translocation; human; human cell; ligation; priority journal; protein expression; protein function; signal transduction; T lymphocyte; animal; cell line; cytology; enzyme activation; lymphocyte activation; metabolism; physiology; protein transport; signal transduction; Animals; Antigens, CD; Antigens, CD43; Antigens, Differentiation, T-Lymphocyte; Cell Line; DNA; DNA-Binding Proteins; Enzyme Activation; Humans; Isoenzymes; Lymphocyte Activation; MAP Kinase Signaling System; NF-kappa B; NFATC Transcription Factors; Nuclear Proteins; Protein Kinase C; Protein Transport; Sialoglycoproteins; T-Lymphocytes; Transcription Factor AP-1; Transcription Factors
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