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

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 Ser 473 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 Ser 473 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.

Original languageEnglish (US)
Article numberra2
JournalScience Signaling
Volume6
Issue number257
DOIs
StatePublished - Jan 8 2013
Externally publishedYes

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Phosphorylation
Adipocytes
Adipogenesis
Chemical activation
Association reactions
Gene encoding
Embryonic Stem Cells
TOR complex 2
Stem cells
Transducers
Intercellular Signaling Peptides and Proteins
Transcription Factors
Genes
Switches
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Yao, Y., Suraokar, M., Darnay, B. G., Hollier, B. G., Shaiken, T. E., Asano, T., ... Reddy, S. A. G. (2013). BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation. Science Signaling, 6(257), [ra2]. https://doi.org/10.1126/scisignal.2003295

BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation. / 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; Sarbassov, Dos; Mani, Sendurai A.; Abbruzzese, James L.; Reddy, Shrikanth A G.

In: Science Signaling, Vol. 6, No. 257, ra2, 08.01.2013.

Research output: Contribution to journalArticle

Yao, Y, Suraokar, M, Darnay, BG, Hollier, BG, Shaiken, TE, Asano, T, Chen, CH, Chang, BHJ, Lu, Y, Mills, G, Sarbassov, D, Mani, SA, Abbruzzese, JL & Reddy, SAG 2013, 'BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation', Science Signaling, vol. 6, no. 257, ra2. https://doi.org/10.1126/scisignal.2003295
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 ; Sarbassov, Dos ; Mani, Sendurai A. ; Abbruzzese, James L. ; Reddy, Shrikanth A G. / BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation. In: Science Signaling. 2013 ; Vol. 6, No. 257.
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