title: Drosophila C-terminal Src kinase regulates growth via the Hippo signaling pathway.
abstract: The Hippo signaling pathway is involved in regulating tissue size by inhibiting cell proliferation and promoting apoptosis. Aberrant Hippo pathway function is often detected in human cancers and correlates with poor prognosis. The Drosophila C-terminal Src kinase (d-Csk) is a genetic modifier of warts (wts), a tumor-suppressor gene in the Hippo pathway, and interacts with the Src oncogene. Reduction in d-Csk expression and the consequent activation of Src are frequently seen in several cancers including hepatocellular and colorectal tumors. Previous studies show that d-Csk regulates cell proliferation and tissue size during development. Given the similarity in the loss-of-function phenotypes of d-Csk and wts, we have investigated the interactions of d-Csk with the Hippo pathway. Here we present multiple lines of evidence suggesting that d-Csk regulates growth via the Hippo signaling pathway. We show that loss of dCsk caused increased Yki activity, and our genetic epistasis places dCsk downstream of Dachs. Furthermore, dCsk requires Yki for its growth regulatory functions, suggesting that dCsk is another upstream member of the network of genes that interact to regulate Wts and its effector Yki in the Hippo signaling pathway.
authors.affiliation: Department of Biology, University of Dayton, Dayton, OH 45469, USA.
authors.forename: Hailey J
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Biology, University of Dayton, Dayton, OH 45469, USA.
authors.forename: Indrayani
authors.initials: I
authors.lastname: Waghmare
authors.affiliation: Department of Biology, University of Dayton, Dayton, OH 45469, USA.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Verghese
authors.affiliation: Centerville High School, Centerville, OH 45459, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Biology, University of Dayton, Dayton, OH 45469, USA; Center for Tissue Regeneration and Engineering at Dayton, Dayton, OH 45469, USA; Premedical Programs, University of Dayton, Dayton, OH 45469, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Biology, University of Dayton, Dayton, OH 45469, USA; Center for Tissue Regeneration and Engineering at Dayton, Dayton, OH 45469, USA; Premedical Programs, University of Dayton, Dayton, OH 45469, USA. Electronic address: mkangosingh1@udayton.edu.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Kango-Singh
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000081247:CSK Tyrosine-Protein Kinase; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development; D000091102:YAP-Signaling Proteins; D060589:Zyxin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D000081247:CSK Tyrosine-Protein Kinase; D029721:Drosophila Proteins; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009218:Myosins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; D060589:Zyxin; D019061:src-Family Kinases; C503814:Yki protein, Drosophila; C499520:Zyx protein, Drosophila; C492999:dachs protein, Drosophila; C000609101:Csk protein, Drosophila; C000631346:CSK protein, human; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: Cell proliferation; Drosophila; Growth; Imaginal discs; Src; Yki; dCsk