| First Author | Park BH | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 1 | Pages | e30983 |
| PubMed ID | 22292086 | Mgi Jnum | J:184223 |
| Mgi Id | MGI:5320520 | Doi | 10.1371/journal.pone.0030983 |
| Citation | Park BH, et al. (2012) Mammalian ste20-like kinase and SAV1 promote 3T3-L1 adipocyte differentiation by activation of PPARgamma. PLoS One 7(1):e30983 |
| abstractText | 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 gamma (PPARgamma), a transcription factor that plays a key role in adipogenesis. The interaction of endogenous SAV1 and PPARgamma 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 PPARgamma. Overexpression of MST2 and SAV1 increased PPARgamma levels by stabilizing the protein, and the knockdown of SAV1 resulted in a decrease of endogenous PPARgamma 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 PPARgamma expression also begins to increase. MST2 and SAV1 significantly increased PPARgamma transactivation, and SAV1 was shown to be required for the activation of PPARgamma 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 PPARgamma activation by the MST signaling pathway may be a novel regulatory mechanism of adipogenesis. |
