The FERM-domain protein Expanded regulates Hippo pathway activity via direct interactions with the transcriptional activator Yorkie

Caroline Badouel, Laura Gardano, Nancy Amin, Ankush Garg, Robyn Rosenfeld, Thierry Le Bihan, Helen McNeill

Research output: Contribution to journalArticlepeer-review

Abstract

The Hippo kinase pathway plays a central role in growth regulation and tumor suppression from flies to man. The Hippo/Mst kinase phosphorylates and activates the NDR family kinase Warts/Lats, which phosphorylates and inhibits the transcriptional activator Yorkie/YAP. Current models place the FERM-domain protein Expanded upstream of Hippo kinase in growth control. To understand how Expanded regulates Hippo pathway activity, we used affinity chromatography and mass spectrometry to identify Expanded-binding proteins. Surprisingly we find that Yorkie is the major Expanded-binding protein in Drosophila S2 cells. Expanded binds Yorkie at endogenous levels via WW-domain-PPxY interactions, independently of Yorkie phosphorylation at S168, which is critical for 14-3-3 binding. Expanded relocalizes Yorkie from the nucleus, abrogating its nuclear activity, and it can regulate growth downstream of warts in vivo. These data lead to a new model whereby Expanded functions downstream of Warts, in concert with 14-3-3 proteins to sequester Yorkie in the cytoplasm, inhibiting growth activity of the Hippo pathway.
Original languageEnglish
Pages (from-to)411-420
JournalDevelopmental Cell
Volume16
Issue number3
Early online date16 Mar 2009
DOIs
Publication statusPublished - 17 Mar 2009

Keywords

  • Signaling

Fingerprint

Dive into the research topics of 'The FERM-domain protein Expanded regulates Hippo pathway activity via direct interactions with the transcriptional activator Yorkie'. Together they form a unique fingerprint.

Cite this