Neuregulin 1-activated ERBB4 as a "dedicated" receptor for the Hippo-YAP pathway.

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.