PKG1α Cysteine-42 Redox State Controls mTORC1 Activation in Pathological Cardiac Hypertrophy.

ABSTRACT:

Rationale

Stimulated PKG1α (protein kinase G-1α) phosphorylates TSC2 (tuberous sclerosis complex 2) at serine 1365, potently suppressing mTORC1 (mechanistic [mammalian] target of rapamycin complex 1) activation by neurohormonal and hemodynamic stress. This reduces pathological hypertrophy and dysfunction and increases autophagy. PKG1α oxidation at cysteine-42 is also induced by these stressors, which blunts its cardioprotective effects.

Objective

We tested the dependence of mTORC1 activation on PKG1α C42 oxidation and its capacity to suppress such activation by soluble GC-1 (guanylyl cyclase 1) activation.

Methods and results

Cardiomyocytes expressing wild-type (WT) PKG1α (PKG1α^WT) or cysteine-42 to serine mutation redox-dead (PKG1α^CS/CS) were ex

SUBMITTER: Oeing CU 

PROVIDER: S-EPMC7416445 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature