Details

Autor(en) / Beteiligte

• Yao, Yixin
• Suraokar, Milind
• Darnay, Bryant G
• Hollier, Brett G
• Shaiken, Tattym E
• Asano, Takayuki
• Chen, Chien-Hung
• Chang, Benny H-J
• Lu, Yiling
• Mills, Gordon B
• Sarbassov, Dos
• Mani, Sendurai A
• Abbruzzese, James L
• Reddy, Shrikanth A G

Titel

BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation

Ist Teil von

• Science signaling, 2013-01, Vol.6 (257), p.ra2

Ort / Verlag

United States

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Phosphorylation and activation of Akt1 is a crucial signaling event that promotes adipogenesis. However, neither the complex multistep process that leads to activation of Akt1 through phosphorylation at Thr³⁰⁸ and Ser⁴⁷³ nor the mechanism by which Akt1 stimulates adipogenesis is fully understood. We found that the BSD domain-containing signal transducer and Akt interactor (BSTA) promoted phosphorylation of Akt1 at Ser⁴⁷³ in various human and murine cells, and we uncovered a function for the BSD domain in BSTA-Akt1 complex formation. The mammalian target of rapamycin complex 2 (mTORC2) facilitated the phosphorylation of BSTA and its association with Akt1, and the BSTA-Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser⁴⁷³ in response to growth factor stimulation. Furthermore, analyses of bsta gene-trap murine embryonic stem cells revealed an essential function for BSTA and phosphorylation of Akt1 at Ser⁴⁷³ in promoting adipocyte differentiation, which required suppression of the expression of the gene encoding the transcription factor FoxC2. These findings indicate that BSTA is a molecular switch that promotes phosphorylation of Akt1 at Ser⁴⁷³ and reveal an mTORC2-BSTA-Akt1-FoxC2-mediated signaling mechanism that is critical for adipocyte differentiation.