Proline-rich AKT1 substrate 1 (PRAS40)

Proline-rich AKT1 substrate 1 (PRAS40) is a protein encoded by the AKT1S1 gene in humans. It is a prominent substrate of the serine/threonine kinase Akt and an interacting partner of 14-3-3 proteins[4][1]. PRAS40 is also a physiological substrate of the mTOR complex 1 (mTORC1), where it binds to the raptor component and is differentially phosphorylated by mTORC1 and Akt[2]. Functionally, PRAS40 serves as a key modulator of cell survival, proliferation, and NF-κB transcriptional activity, particularly by promoting NF-κB’s transcriptional output and supporting cancer cell growth and survival[3]. It is upregulated and phosphorylated in various cancers, with evidence of altered activity in tumors with p53 and Ras mutations, making it a potential biomarker for early carcinogenesis[1].

Other names

AKT1S1LobeProline-rich Akt substrate of 40 kDaProline-rich Akt-substrate PRAS40

Inhibitors may regulate mTORC1 signaling via modulation of PRAS40 phosphorylation and interaction