title: Neuregulin 1-activated ERBB4 as a "dedicated" receptor for the Hippo-YAP pathway.
abstract: The Hippo tumor-suppressor pathway is regulated by several multicomponent complexes of cell polarity and cell-to-cell junctions. Hippo kinases inhibit the transcription coactivator YAP. In contrast to the orthologous pathway in Drosophila, in which the single transmembrane receptor Fat and its ligand Dachsous are "dedicated" to trigger the pathway, the mammalian Hippo-YAP pathway was without such a dedicated receptor. In this issue of Science Signaling, a study by Haskins et al. has brought an end to this scenario of an "orphaned" pathway by identifying neuregulin 1 and its cognate receptor ERBB4 [epidermal growth factor receptor (EGFR) family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4] as a major receptor complex that activates YAP activity. Moreover, the identification of ERBB4 as a dominant receptor of YAP signaling brings into focus the signaling interface between the EGFR signaling axis and the Hippo-YAP network, with numerous implications for basic and applied cancer research.
authors.affiliation: Department of Physiology, National University of Singapore, Laboratory of Cancer Signaling and Domainopathies, Yong Loo Li School of Medicine, Block MD9, 2 Medical Drive 04-01, Singapore 117597, Republic of Singapore. Mechanobiology Institute, T-Lab, 5-01, 5A Engineering Drive 1, Singapore 117411, Republic of Singapore. Institute of Molecular and Cell Biology A*STAR, 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore. phsms@nus.edu.sg.
authors.forename: Marius
authors.initials: M
authors.lastname: Sudol
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D000090683:Hippo Signaling Pathway; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D066247:Receptor, ErbB-4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C094131:NRG1 protein, human; D020890:Neuregulin-1; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; C587689:ERBB4 protein, human; D066247:Receptor, ErbB-4; D017346:Protein Serine-Threonine Kinases