Homeostatic control of Hippo signaling activity revealed by an endogenous activating mutation in YAP.

ABSTRACT: The Hippo signaling pathway converges on YAP to regulate growth, differentiation, and regeneration. Previous studies with overexpressed proteins have shown that YAP is phosphorylated by its upstream kinase, Lats1/2, on multiple sites, including an evolutionarily conserved 14-3-3-binding site whose phosphorylation is believed to inhibit YAP by excluding it from the nucleus. Indeed, nuclear localization of YAP or decreased YAP phosphorylation at this site (S168 in Drosophila, S127 in humans, and S112 in mice) is widely used in current literature as a surrogate of YAP activation even though the physiological importance of this phosphorylation event in regulating endogenous YAP activity has not been defined. Here we address this question by introducing a Yap(S112A) knock-in mutation in the end

SUBMITTER: Chen Q 

PROVIDER: S-EPMC4495399 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature