A protein interaction map for cell-cell adhesion regulators identifies DUSP23 as a novel phosphatase for β-catenin

• DOI: 10.1038/srep27114
• Publication Date: 2016-06-03T10:42:35Z
• Authors: Lisa Leon Gallegos; Mei Rosa Ng; Mathew E. Sowa; Laura M. Selfors; Anne White; Ioannis K. Zervan...; Pragya Singh; Sabin Dhakal; J. Wade Harper; Joan S. Brugge
• Keywords: Adherens junction; Plakoglobin; Cell–cell interaction

Abstract Cell-cell adhesion is central to morphogenesis and maintenance of epithelial cell state. We previously identified 27 candidate cell-cell regulatory proteins (CCARPs) whose down-regulation disrupts during collective migration. Using a protein interaction mapping strategy, we found that 18 CCARPs link core components adherens junctions or desmosomes. further mapped linkages between the other known proteins, including hits from recent screens uncovering novel E-cadherin adhesions. Mechanistic studies one CCARP which links multiple phosphatase DUSP23, revealed it promotes dephosphorylation β-catenin at Tyr 142 enhances α- β-catenin. DUSP23 knockdown specifically diminished without altering fibronectin matrix proteins. Furthermore, produced “zipper-like” adhesions, caused defects in transmission polarization cues, reduced coordination Thus, this study identifies connections regulate interactions provides evidence for unrecognized role regulating through promoting