Identification of c-Jun NH2-terminal protein kinase (JNK)-activating kinase 2 as an activator of JNK but not p38.
c-Jun NH2-terminal protein kinase (JNK), a distant member of the mitogen-activated protein (MAP) kinase family, regulates gene expression in response to various extracellular stimuli. JNK is activated by JNK-activating kinase 1 (JNKK1), a dual specificity protein kinase that phosphorylates JNK on threonine 183 and tyrosine 185 residues. Here we show that JNKK2, a novel member of the MAP kinase kinase family, was phosphorylated and activated by MEKK1, a MAP kinase kinase kinase in the JNK signaling cascade. JNKK2 activity was also stimulated by constitutively active forms of Rac and Cdc42Hs, members of the Rho small GTP-binding protein family. Unlike JNKK1 that activates both JNK and p38 MAP kinases, JNKK2 stimulated only JNK. Transient transfection assays demonstrated that JNKK2 potentiated the stimulation of c-Jun transcriptional activity by MEKK1. The existence of multiple JNK-activating kinases may contribute to the specificity of the JNK signaling cascade.
Lu
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Department of Pathology, Division of Molecular and Cellular Pathology, the University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Nemoto
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Lin
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A
D000595:Amino Acid Sequence; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; D048728:MAP Kinase Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases