AKT1S1 (PRAS40) is phosphorylated by AKT at Thr246, which...

AKT1S1 (PRAS40) is phosphorylated by AKT at Thr246, which leads to the binding of YWHAB (14-3-3 beta) (Zhang et al. 2002, Kovacina et al. 2003). AKT1S1 is phosphorylated at Ser183 (Oshiro et al. 2007; Wang et al. 2008; Yun et al. 2016) and Ser221 (Wang et al. 2008; Yun et al. 2016) by the mTORC1 complex, which further inhibits the association of AKT1S1 with the mTORC1 complex and promotes binding to YWHAB (Oshiro et al. 2007; Wang et al. 2008). The mTORC1 complex was also reported to phosphorylate AKT1S1 on Ser212, but phosphorylation at this site does not appear to be functionally significant (Wang et al. 2008). Sequestration of AKT1S1 by YWHAB facilitates binding of the mTORC1 complex to its substrates, such as RPS6KB1 and 4E-BP1 (Wang et al. 2012). Phosphorylation of AKT1S1 by the mTORC1 complex has been reported to regulate formation of immunoproteasomes (Yun et al. 2016).

AKT1S1 shuttles between the cytosol and the nucleus (Havel et al. 2015). In the nucleus, AKT1S1 phosphorylated at Thr246 and Ser221 binds to the nuclear protein RPL11 and may participate in the RPL11-MDM2-TP53 nucleolar stress response pathway (Havel et al. 2015).

Excessive phosphorylation of AKT1S1 by AKT and mTORC1 may contribute to pathological myocardial hypertrophy (Völkers et al. 2013).