V-Akt Murine Thymoma Viral Oncogene Homolog 1 Substrate 1 (AKT1S1)

AKT1S1 is a proline-rich substrate of AKT that binds 14-3-3 protein when phosphorylated. The deduced 256-amino acid human protein contains 2 N-terminal proline-rich regions and a C-terminal AKT phosphorylation site, thr246, that is conserved in rat and mouse. Northern blot analysis detected 2.6- and 1.8-kb PRAS40 transcripts in all tissues examined, with highest levels of both transcripts in liver and heart. EST database analysis suggested that these 2 transcripts are splice variants with identical coding regions.Phosphorylation induced by constitutively active AKT was not blocked by a PI3K/AKT inhibitor, unlike that induced by wildtype AKT. Mutation analysis showed that phosphorylation of PRAS40 by AKT occurred at thr246. PRAS40 and 14-3-3 protein coimmunoprecipitated in transfected HEK293 cells.