Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases

Abstract

Significance This study defines a unique mechanism controlling the activation of Hippo signaling and consequent inhibition of cell growth. Specifically, serum starvation is found to induce the large tumor suppressor (LATS)1/2 kinases to phosphorylate and thus stabilize the 130 kDa isoform of the membrane-associated polarity protein angiomotin (Amot130). As a consequence, Amot130 recruits the E3 protein-ubiquitin ligase atrophin-1 interacting protein 4. This multiprotein complex then signals the degradation of Yes-associated protein (YAP) and the inhibition of cell growth. These findings significantly modify our current view that YAP phosphorylation by LATS1/2 is sufficient for its inhibition in mammals and thus for growth arrest.