title: Overlapping functions of the MAP4K family kinases Hppy and Msn in Hippo signaling.
abstract: The Hippo (Hpo) tumor suppressor pathway is an evolutionarily conserved signaling pathway that controls tissue growth and organ size in species ranging from Drosophila to human, and its malfunction has been implicated in many types of human cancer. In this study, we conducted a kinome screen and identified Happyhour (Hppy)/MAP4K3 as a novel player in the Hpo pathway. Our biochemical study showed that Hppy binds and phosphorylates Wts. Our genetic experiments suggest that Hppy acts in parallel and partial redundantly with Misshapen (Msn)/MAP4K4 to regulate Yki nuclear localization and Hpo target gene expression in Drosophila wing imaginal discs. Furthermore, we showed that cytoskeleton stress restricts Yki nuclear localization through Hppy and Msn when Hpo activity is compromised, thus providing an explanation for the Wts-dependent but Hpo-independent regulation of Yki in certain contexts. Our study has unraveled an additional layer of complexity in the Hpo signaling pathway and laid down a foundation for exploring how different upstream regulators feed into the core Hpo pathway.
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallars, TX, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallars, TX, USA.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallars, TX, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallars, TX, USA.
authors.forename: Yong Suk
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallars, TX, USA; Center for the genetics and Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Yue
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School , Worcester, MA, USA.
authors.forename: Y Tony
authors.initials: YT
authors.lastname: Ip
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallars, TX, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallars, TX, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallars, TX, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Jiang
keywords: Hippo; ISC; MAP4K; Wts; Yki; organ size