Abstract
The predominant expression of protein kinase C (PKC) theta in T cells (J. Biol. Chem. 1993. 268: 4997-5004), its isoenzyme-specific ability to stimulate AP-1 transcriptional activity (Mol. Cell. Biol. 1996. 16: 1842-1850) and the recent discovery of its selective and antigen-dependent colocalization with the contact region between T cells and antigen-presenting cells (Nature 1997. 385: 83-89) suggest that, among the PKC family members, PKCtheta plays a specialized role in T cell activation. By investigating the downstream effectors of PKCtheta we now demonstrate a direct and isoenzyme-specific contribution of PKCtheta to c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) but not extracellular regulated kinase (ERK) activation. Expression of a constitutively active (CA) form of PKCtheta (but not CA-PKCalpha, epsilon and lambda/iota) resulted in strong activation of JNK/SAPK and expression of a dominant-negative form of PKCtheta interfered with the endogenous activation signal for JNK/SAPK. Importantly, Ca2+ ionophore and CA-PKCtheta (but not CA-PKCalpha, epsilon and lambda/iota) caused synergistic activation of the IL-2 promoter. Together, these data establish that PKCtheta is required for activation of JNK/SAPK signaling leading to IL-2 promoter transcription in T lymphocytes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anisomycin / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Enzyme Activation / drug effects
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Fetal Proteins / metabolism
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Gene Expression Regulation, Enzymologic
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Humans
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Interleukin-2 / genetics*
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Ionomycin / pharmacology
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Isoenzymes / genetics
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Isoenzymes / metabolism*
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JNK Mitogen-Activated Protein Kinases
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Jurkat Cells
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Lymphocyte Activation
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MAP Kinase Kinase Kinase 1*
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Mitogen-Activated Protein Kinases / metabolism
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Promoter Regions, Genetic*
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Protein Kinase C / genetics
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Protein Kinase C / metabolism*
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Protein Kinase C-theta
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Protein Serine-Threonine Kinases / metabolism
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Receptor Protein-Tyrosine Kinases
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Receptor, EphA4
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T-Lymphocytes / drug effects
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T-Lymphocytes / enzymology*
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T-Lymphocytes / immunology*
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Tetradecanoylphorbol Acetate / pharmacology
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Transfection
Substances
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Fetal Proteins
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Interleukin-2
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Isoenzymes
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Ionomycin
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Anisomycin
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Receptor Protein-Tyrosine Kinases
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Receptor, EphA4
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Protein Serine-Threonine Kinases
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PRKCQ protein, human
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Protein Kinase C
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Protein Kinase C-theta
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 1
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MAP3K1 protein, human
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Tetradecanoylphorbol Acetate