Drosophila C-terminal Src kinase negatively regulates organ growth and cell proliferation through inhibition of the Src, Jun N-terminal kinase, and STAT pathways.
Src family kinases regulate multiple cellular processes including proliferation and oncogenesis. C-terminal Src kinase (Csk) encodes a critical negative regulator of Src family kinases. We demonstrate that the Drosophila melanogaster Csk ortholog, dCsk, functions as a tumor suppressor: dCsk mutants display organ overgrowth and excess cellular proliferation. Genetic analysis indicates that the dCsk(-/-) overgrowth phenotype results from activation of Src, Jun kinase, and STAT signal transduction pathways. In particular, blockade of STAT function in dCsk mutants severely reduced Src-dependent overgrowth and activated apoptosis of mutant tissue. Our data provide in vivo evidence that Src activity requires JNK and STAT function.
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Renee D
RD
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Bach
Erika A
EA
Cagan
Ross L
RL
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002453:Cell Cycle; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila; D029721:Drosophila Proteins; D020224:Expressed Sequence Tags; D005434:Flow Cytometry; D005838:Genotype; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases; D007814:Larva / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry*; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics; D019061:src-Family Kinases / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C000609101:Csk protein, Drosophila; D019061:src-Family Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases