Fig 1: Model of the SGK3 signaling pathway.(A) IGF1 stimulates the production of PtdIns(3)P by the Class I and class III Vps34 at the endosomes where SGK3 can be recruited and activated by PDK1 and mTORC2 [22]. Once activated SGK3 phosphorylates its selective substrates STX7 and STX12 that are involved in the endocytic pathway. Phosphorylation of STX12 at Ser 139 by SGK3 that is located just beyond the N-terminal Habc regulatory domain promotes interaction with the t-SNARE proteins syntaxin 6 and Vti1a and the v-SNARE protein VAMP4. Our data suggest that this promotes plasma membrane localization. We propose that assessing phosphorylation of STX7 (Ser126) and STX12 (Ser139) that are specific substrates for SGK2 could be used as key biomarkers for the SGK3 signaling pathway.