The Tyrosine Phosphatase PTPN14 Is a Negative Regulator of YAP Activity

被引：72

作者：

Michaloglou, Chrysiis ^{[1
]}

Lehmann, Waltraut ^{[1
]}

Martin, Typhaine ^{[1
]}

Delaunay, Clara ^{[1
]}

Hueber, Andreas ^{[1
]}

Barys, Louise ^{[1
]}

Niu, Honglin ^{[3
]}

Billy, Eric ^{[1
]}

Wartmann, Markus ^{[1
]}

Ito, Moriko ^{[1
]}

Wilson, Christopher J. ^{[2
]}

Digan, Mary Ellen ^{[3
]}

Bauer, Andreas ^{[1
]}

Voshol, Hans ^{[1
]}

Christofori, Gerhard ^{[4
]}

Sellers, William R. ^{[2
]}

Hofmann, Francesco ^{[1
]}

Schmelzle, Tobias ^{[1
]}

机构：

[1] Novartis Inst BioMed Res, Basel, Switzerland

[2] Novartis Inst BioMed Res, Cambridge, MA USA

[3] Novartis Inst BioMed Res, Ctr Prote Chem, Cambridge, MA USA

[4] Univ Basel, Dept Biomed, Inst Biochem & Genet, Basel, Switzerland

来源：

PLOS ONE | 2013年 / 8卷 / 04期

关键词：

YES-ASSOCIATED PROTEIN; HIPPO SIGNALING PATHWAY; CELL-PROLIFERATION; ORGAN SIZE; WW DOMAIN; TUMOR-SUPPRESSOR; DROSOPHILA; APOPTOSIS; ANGIOMOTIN; JUNCTIONS;

D O I：

10.1371/journal.pone.0061916

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

共 41 条

[1] Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis [J].