title: The tyrosine phosphatase PTPN14 is a negative regulator of YAP activity.
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.
authors.affiliation: Novartis Institutes for BioMedical Research, Disease Area Oncology, Basel, Switzerland.
authors.forename: Chrysiis
authors.initials: C
authors.lastname: Michaloglou
authors.forename: Waltraut
authors.initials: W
authors.lastname: Lehmann
authors.forename: Typhaine
authors.initials: T
authors.lastname: Martin
authors.forename: Clara
authors.initials: C
authors.lastname: Delaunay
authors.forename: Andreas
authors.initials: A
authors.lastname: Hueber
authors.forename: Louise
authors.initials: L
authors.lastname: Barys
authors.forename: Honglin
authors.initials: H
authors.lastname: Niu
authors.forename: Eric
authors.initials: E
authors.lastname: Billy
authors.forename: Markus
authors.initials: M
authors.lastname: Wartmann
authors.forename: Moriko
authors.initials: M
authors.lastname: Ito
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wilson
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Digan
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauer
authors.forename: Hans
authors.initials: H
authors.lastname: Voshol
authors.forename: Gerhard
authors.initials: G
authors.lastname: Christofori
authors.forename: William R
authors.initials: WR
authors.lastname: Sellers
authors.forename: Francesco
authors.initials: F
authors.lastname: Hofmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmelzle
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D010750:Phosphoproteins; C093261:PTPN14 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor