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The tyrosine phosphatase PTPN14 is a negative regulator of YAP activity

Michaloglou, C. and Lehmann, W. and Martin, T. and Delaunay, C. and Hueber, A. and Barys, L. and Niu, H. and Billy, E. and Wartmann, M. and Ito, M. and Wilson, C. J. and Digan, M. E. and Bauer, A. and Voshol, H. and Christofori, G. and Sellers, W. R. and Hofmann, F. and Schmelzle, T.. (2013) The tyrosine phosphatase PTPN14 is a negative regulator of YAP activity. PLoS ONE, Vol. 8, H. 4 , e61916.

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Official URL: http://edoc.unibas.ch/dok/A6338674

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
UniBasel Contributors:Christofori, Gerhard M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Aug 2018 06:39
Deposited On:10 Apr 2015 09:13

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