Open AccessPhosphorylation at distinct subcellular locations underlies specificity in mTORC2 activation of SGK1 and Akt
Author(s) -
Catherine E. Gleason,
Juan Oses-Prieto,
Kathy H. Li,
Biswarup Saha,
Gavin Situ,
Alma L. Burlingame,
David Pearce
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.224931
Subject(s) - mtorc2 , phosphorylation , sgk1 , biology , microbiology and biotechnology , protein kinase b , subcellular localization , mtorc1 , cytoplasm
mTORC2 lies at the intersection of signaling pathways that control metabolism and ion transport through phosphorylation of the AGC-family kinases, Akt and SGK1. How mTORC2 targets these functionally distinct downstream effectors in a context-specific manner is not known. Here, we show that the salt- and blood pressure-regulatory hormone, angiotensin II stimulates selective mTORC2-dependent phosphorylation of SGK1 (S422) but not Akt (S473). Conventional PKC (cPKC), a critical mediator of AT1R signaling, regulates the subcellular localization of SIN1 and SGK1. Inhibition of cPKC catalytic activity disturbs SIN1 and SGK1 subcellular localization, re-localizing them from the nucleus and a peri-nuclear compartment to the plasma membrane in advance of hormonal stimulation. Surprisingly, pre-targeting of SIN1 and SGK1 to the plasma membrane prevents SGK1 S422 but not Akt S473 phosphorylation. Additionally, we identify three sites on SIN1 (S128, S315 and S356) phosphorylated in response to cPKC activation. Collectively, these data demonstrate that SGK1 activation occurs at a distinct subcellular compartment from Akt and suggests a mechanism for the selective activation of these functionally distinct mTORC2 targets through subcellular partitioning of mTORC2 activity.