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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

2013; National Academy of Sciences; Volume: 110; Issue: 43 Linguagem: Inglês

10.1073/pnas.1308236110

1091-6490

Jacob J. Adler, Derrick E. Johnson, Brigitte Heller, Lauren R. Bringman, William P. Ranahan, Michael Conwell, Yang Sun, Andy Hudmon, Clark D. Wells,

Plant Surface Properties and Treatments

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.