title: Mammalian ste20-like kinase and SAV1 promote 3T3-L1 adipocyte differentiation by activation of PPARγ.
abstract: The mammalian ste20 kinase (MST) signaling pathway plays an important role in the regulation of apoptosis and cell cycle control. We sought to understand the role of MST2 kinase and Salvador homolog 1 (SAV1), a scaffolding protein that functions in the MST pathway, in adipocyte differentiation. MST2 and MST1 stimulated the binding of SAV1 to peroxisome proliferator-activated receptor γ (PPARγ), a transcription factor that plays a key role in adipogenesis. The interaction of endogenous SAV1 and PPARγ was detected in differentiating 3T3-L1 adipocytes. This binding required the kinase activity of MST2 and was mediated by the WW domains of SAV1 and the PPYY motif of PPARγ. Overexpression of MST2 and SAV1 increased PPARγ levels by stabilizing the protein, and the knockdown of SAV1 resulted in a decrease of endogenous PPARγ protein in 3T3-L1 adipocytes. During the differentiation of 3T3-L1 cells into adipocytes, MST2 and SAV1 expression began to increase at 2 days when PPARγ expression also begins to increase. MST2 and SAV1 significantly increased PPARγ transactivation, and SAV1 was shown to be required for the activation of PPARγ by rosiglitazone. Finally, differentiation of 3T3-L1 cells was augmented by MST2 and SAV1 expression and inhibited by knockdown of MST1/2 or SAV1. These results suggest that PPARγ activation by the MST signaling pathway may be a novel regulatory mechanism of adipogenesis.
authors.affiliation: Department of Biochemistry, College of Medicine, Chungbuk National University, Chungbuk, Korea.
authors.forename: Byoung Hee
authors.initials: BH
authors.lastname: Park
authors.forename: Dae Soon
authors.initials: DS
authors.lastname: Kim
authors.forename: Gun Woo
authors.initials: GW
authors.lastname: Won
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Jeon
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Oh
authors.forename: YoungJoo
authors.initials: Y
authors.lastname: Lee
authors.forename: Eung-Gook
authors.initials: EG
authors.lastname: Kim
authors.forename: Yong Hee
authors.initials: YH
authors.lastname: Lee
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055550:Protein Stability; D000090742:Serine-Threonine Kinase 3; D000099317:Hippo Kinases
chemical_list: D018797:Cell Cycle Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D047495:PPAR gamma; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; C485935:Sav1 protein, mouse; C490818:Stk3 protein, mouse; D000099317:Hippo Kinases