MAPKKK6, a novel mitogen-activated protein kinase kinase kinase, that associates with MAPKKK5.
MAPKKK5/ASK1 activates c-Jun N-terminal kinase (JNK) and p38 kinase signaling pathways and induces apoptosis when expressed in stably transfected cells. Using MAPKKK5 as bait in yeast two-hybrid screening, a novel protein that interacts with MAPKKK5 was identified and cloned. This novel protein is predicted to contain all 11 kinase subdomains and shares 45% amino acid identity with MAPKKK5 and thus is designated MAPKKK6. The interaction of MAPKKK6 with MAPKKK5 in vivo was confirmed by coexpression of MAPKKK5 and MAPKKK6 in 293 cells followed by immunoprecipitation. In contrast to MAPKKK5, which activated both JNK and p38 kinase pathways, MAPKKK6 only weakly activated JNK but not ERK or p38 kinase pathways.
Wang
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Amgen, Incorporated, Boulder, Colorado 80301, USA.
Diener
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Tan
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Yao
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D000595:Amino Acid Sequence; D001921:Brain; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D006367:HeLa Cells; D006321:Heart; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases; C116394:MAP kinase kinase kinase 6; C482858:MAP3K5 protein, human