From cell structure to transcription: Hippo forges a new path.
The control of cell number during animal development is a longstanding puzzle. Recent studies in the fruit fly Drosophila melanogaster have defined a new signaling pathway that restricts cell proliferation in differentiating epithelia. The cytoskeletal proteins Merlin and Expanded, which play a role in cell adhesion and structure, control the activation of the Hippo/Salvador kinase complex, which in turn activates the Warts/Mats kinase complex. Warts/Mats kinase phosphorylates and inhibits Yorkie, a transcriptional coactivator that positively regulates cell growth, survival, and proliferation. This conserved signaling pathway contains several tumor-suppressor genes and regulates the contact inhibition of proliferation in cultured cells.
Edgar
Bruce A
BA
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA. bedgar@fhcrc.org
D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology*; D005786:Gene Expression Regulation / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000099317:Hippo Kinases
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C465504:sav protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases