Upstream regulation of the hippo size control pathway.
The newly discovered Salvador-Warts-Hippo (SWH) pathway is a key regulator of tissue growth during both development and disease. The first identified components of this pathway represent core downstream effector proteins: the kinases Warts and Hippo; the adaptor proteins Salvador and Mats; and the transcriptional co-activator Yorkie. More recently, a surprising number of proteins have been implicated as upstream regulators of the SWH pathway, including: the planar cell polarity cadherins Fat and Dachsous; the FERM-domain proteins Expanded and Merlin; the WW-domain protein Kibra; the Ras-association family protein dRASSF; and the apicobasal polarity proteins lethal giant larvae, atypical protein kinase C and Crumbs. The identification of a large cohort of upstream regulatory proteins suggests that core SWH pathway proteins are poised to respond to diverse stimuli that must be integrated in a coordinated fashion. Here, we review the existing knowledge of upstream SWH pathway proteins and discuss possible mechanisms of action and signal integration.
Grusche
Felix A
FA
Cell Growth and Proliferation Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Richardson
Helena E
HE
Harvey
Kieran F
KF
D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D000099317:Hippo Kinases
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases