The Phosphatase CSW Controls Life Span by Insulin Signaling and Metabolism Throughout Adult Life in Drosophila.

ABSTRACT: Noonan syndrome and related disorders are caused by mutations in genes encoding for proteins of the RAS-ERK1/2 signaling pathway, which affect development by enhanced ERK1/2 activity. However, the mutations' effects throughout adult life are unclear. In this study, we identify that the protein most commonly affected in Noonan syndrome, the phosphatase SHP2, known in Drosophila as corkscrew (CSW), controls life span, triglyceride levels, and metabolism without affecting ERK signaling pathway. We found that CSW loss-of-function mutations extended life span by interacting with components of the insulin signaling pathway and impairing AKT activity in adult flies. By expressing csw-RNAi in different organs, we determined that CSW extended life span by acting in organs that

SUBMITTER: Ruzzi LR 

PROVIDER: S-EPMC7221067 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature