Abstract
Previously we implicated c-Jun N-terminal kinase (JNK) as an element that is involved in signal integration during co-stimulation of T lymphocytes. This pathway has now been traced to an upper level, comprising MAPKK SEK1/MKK4/JNKK1 which, similarly to JNK, must receive input both from the TCR and CD28. A large portion of this input is probably integrated at the level of the Rho-family protein CDC42 which, here, activates SEK1 and JNK to the level reached by TCR and CD28 stimulation. We have identified another putative SEK/ JNK pathway regulator, PKCtheta, which in contrast to CDC42, activates SEK and JNK maximally only in conjunction with a calcium signal delivered through calcineurin. Signals originating at the TCR and CD28 may travel down the JNK pathway via PKCtheta, calcineurin, CDC42, MEKK1 and SEK1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcineurin / genetics
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Calcineurin / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Cycle Proteins / metabolism
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Enzyme Activation
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GTP-Binding Proteins / metabolism
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Humans
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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 4*
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Mice
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Mitogen-Activated Protein Kinase Kinases*
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Mitogen-Activated Protein Kinases*
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Mutation
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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 Kinases / genetics
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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Signal Transduction
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T-Lymphocytes / enzymology*
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T-Lymphocytes / immunology
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Transfection
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cdc42 GTP-Binding Protein
Substances
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Cell Cycle Proteins
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Isoenzymes
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Protein Kinases
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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PRKCQ protein, human
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Prkcq protein, mouse
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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 4
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MAP2K4 protein, human
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Map2k4 protein, mouse
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Mitogen-Activated Protein Kinase Kinases
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Calcineurin
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GTP-Binding Proteins
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cdc42 GTP-Binding Protein