Work

In vivo regulation of Yorkie phosphorylation and localization

Year: 2008

Type: article

Abstract: Yorkie (Yki), a transcription factor of the Fat and Hippo signaling pathways, is negatively regulated by the Warts kinase. Here, we use Phos-tag gels to characterize Warts-dependent phosphorylation of Yki in vivo, and show that Warts promotes phosphorylation of Yki at multiple sites. We also show that Warts inhibits Yki nuclear localization in vivo, and can promote binding of Yki to 14-3-3 proteins in cultured cells. In vivo assessment of the influence of individual upstream regulators of Warts reveals that some mutants (e.g. fat) have only partial effects on Yki phosphorylation, and weak effects on Yki localization, whereas other genotypes (e.g. ex fat double mutants) have stronger effects on both Yki phosphorylation and localization. We also identify serine 168 as a critical site through which negative regulation of Yki by Warts-mediated phosphorylation occurs, but find that this site is not sufficient to explain effects of Hippo signaling on Yki in vivo. These results identify modulation of subcellular localization as a mechanism of Yki regulation, and establish that this regulation occurs in vivo through multiple sites of Warts-dependent phosphorylation on Yki.

Source: Development

DOI: 10.1242/dev.015255

Authors: Hyangyee Oh, Kenneth D. Irvine

Institutions: Rutgers, The State University of New Jersey, Howard Hughes Medical Institute

Language: English

Topic: Hippo pathway signaling and YAP/TAZ

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Howard Hughes Medical Institute, National Institutes of Health, National Institute of General Medical Sciences

Awards: G2696048491, Transcriptional regulation of growth downstream of tumor suppressor pathways, G942653713