Title |
The Tyrosine Phosphatase PTPN14 Is a Negative Regulator of YAP Activity
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Published in |
PLOS ONE, April 2013
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DOI | 10.1371/journal.pone.0061916 |
Pubmed ID | |
Authors |
Chrysiis Michaloglou, Waltraut Lehmann, Typhaine Martin, Clara Delaunay, Andreas Hueber, Louise Barys, Honglin Niu, Eric Billy, Markus Wartmann, Moriko Ito, Christopher J. Wilson, Mary Ellen Digan, Andreas Bauer, Hans Voshol, Gerhard Christofori, William R. Sellers, Francesco Hofmann, Tobias Schmelzle |
Abstract |
The Hippo (Hpo) pathway is a novel signaling pathway that controls organ size in Drosophila and mammals and is deregulated in a variety of human cancers. It consists of a set of kinases that, through a number of phosphorylation events, inactivate YAP, a transcriptional co-activator that controls cellular proliferation and apoptosis. We have identified PTPN14 as a YAP-binding protein that negatively regulates YAP activity by controlling its localization. Mechanistically, we find that the interaction of ectopic YAP with PTPN14 can be mediated by the respective WW and PPxY motifs. However, the PTPN14 PPxY motif and phosphatase activity appear to be dispensable for the negative regulation of endogenous YAP, likely suggesting more complex mechanisms of interaction and modulation. Finally, we demonstrate that PTPN14 downregulation can phenocopy YAP activation in mammary epithelial cells and synergize with YAP to induce oncogenic transformation. |
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Student > Master | 4 | 6% |
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Immunology and Microbiology | 1 | 1% |
Other | 3 | 4% |
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