PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress.

ABSTRACT: The mechanistic target of rapamycin complex-1 (mTORC1) coordinates regulation of growth, metabolism, protein synthesis and autophagy¹. Its hyperactivation contributes to disease in numerous organs, including the heart^1,2, although broad inhibition of mTORC1 risks interference with its homeostatic roles. Tuberin (TSC2) is a GTPase-activating protein and prominent intrinsic regulator of mTORC1 that acts through modulation of RHEB (Ras homologue enriched in brain). TSC2 constitutively inhibits mTORC1; however, this activity is modified by phosphorylation from multiple signalling kinases that in turn inhibits (AMPK and GSK-3β) or stimulates (AKT, ERK and RSK-1) mTORC1 activity^3-9. Each kinase requires engagement of multiple serines, impeding analysis of their r

SUBMITTER: Ranek MJ 

PROVIDER: S-EPMC6426636 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature