title: Coordinate Activation of Redox-Dependent ASK1/TGF-β Signaling by a Multiprotein Complex (MPK38, ASK1, SMADs, ZPR9, and TRX) Improves Glucose and Lipid Metabolism in Mice.
abstract: OBJECTIVE
  To explore the molecular connections between redox-dependent apoptosis signal-regulating kinase 1 (ASK1) and transforming growth factor-β (TGF-β) signaling pathways and to examine the physiological processes in which coordinated regulation of these two signaling pathways plays a critical role.
  
  
  RESULTS
  We provide evidence that the ASK1 and TGF-β signaling pathways are interconnected by a multiprotein complex harboring murine protein serine-threonine kinase 38 (MPK38), ASK1, Sma- and Mad-related proteins (SMADs), zinc-finger-like protein 9 (ZPR9), and thioredoxin (TRX) and demonstrate that the activation of either ASK1 or TGF-β activity is sufficient to activate both the redox-dependent ASK1 and TGF-β signaling pathways. Physiologically, the restoration of the downregulated activation levels of ASK1 and TGF-β signaling in genetically and diet-induced obese mice by adenoviral delivery of SMAD3 or ZPR9 results in the amelioration of adiposity, hyperglycemia, hyperlipidemia, and impaired ketogenesis.
  
  
  CONCLUSIONS
  Our data suggest that the multiprotein complex linking ASK1 and TGF-β signaling pathways may be a potential target for redox-mediated metabolic complications.
authors.affiliation: Department of Biochemistry, School of Life Sciences, Chungbuk National University , Cheongju, Korea.
authors.forename: Hyun-A
authors.initials: HA
authors.lastname: Seong
authors.affiliation: Department of Biochemistry, School of Life Sciences, Chungbuk National University , Cheongju, Korea.
authors.forename: Ravi
authors.initials: R
authors.lastname: Manoharan
authors.affiliation: Department of Biochemistry, School of Life Sciences, Chungbuk National University , Cheongju, Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Ha
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D016212:Transforming Growth Factor beta; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse; D005947:Glucose