title: A subdomain of MEKK1 that is critical for binding to MKK4.
abstract: Mitogen-activated protein kinase (MAPK) cascades are central components of signal transduction pathways induced by mitogens and stresses. They consist of a three-kinase module in which a mitogen-activated protein kinase kinase kinase (MAP3K) activates a mitogen-activated protein kinase kinase (MAP2K), which in turn activates MAPK. The molecular determinants that underlie specific MAP3K-MAP2K interactions are poorly understood. In this study, we examined the interaction between the MAP3K MEKK1 and MKK4, a MAP2K of the JNK pathway. Select point mutations in subdomain X of the catalytic domain of MEKK1 (MEKK1delta) were found to impair the ability of MEKK1delta to bind to and activate MKK4. Such mutations were also found to impair MEKK1delta-induced activation of an AP1 reporter gene. These studies point to a critical role for subdomain X in the interaction of MEKK1 with MKK4.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 605 Stellar Chance Labs, 422 Curie Blvd, Philadelphia, PA 19104, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tu
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Mooney
authors.forename: Frank S
authors.initials: FS
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D020134:Catalytic Domain; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase; D048369:MAP Kinase Kinase 1; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; D048728:MAP Kinase Kinase Kinase 1; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D016415:Sequence Alignment; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; C482578:Map3k1 protein, mouse; D048369:MAP Kinase Kinase 1; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482125:MAP2K1 protein, human; C482559:MAP2K4 protein, human; C482569:MAP2K7 protein, human; C482127:Map2k1 protein, mouse; C482562:Map2k4 protein, mouse; C482570:Map2k7 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases