1. Drosophila Src-family kinases function with Csk to regulate cell proliferation and apoptosis.
- Author
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Pedraza LG, Stewart RA, Li DM, and Xu T
- Subjects
- Animals, CSK Tyrosine-Protein Kinase, Cell Division physiology, Cloning, Molecular, Drosophila enzymology, Enzyme Activation, Eye embryology, Eye ultrastructure, Glutathione Transferase metabolism, Larva, Microscopy, Electron, Scanning, Mutation, Recombinant Fusion Proteins metabolism, Apoptosis, Cell Division genetics, Drosophila genetics, Drosophila Proteins metabolism, Membrane Proteins metabolism, Phosphoproteins metabolism, src-Family Kinases metabolism
- Abstract
Elevated Src protein levels and activity are associated with the development and progression of a variety of cancers. The consequences of deregulated Src activity have been studied extensively in cell culture; however, the effects of this deregulation in vivo, as well as the mechanisms of Src-induced tumorigenesis, remain poorly understood. In this study, the effect of expressing wild-type and constitutively active Drosophila Src-family kinases (SFKs) in the developing eye was examined. Overexpression of either wild-type Drosophila SFK (Src64 and Src42) is sufficient to induce ectopic proliferation in G1/G0-arrested, uncommitted cells in eye imaginal discs. In addition, both kinases trigger apoptosis in vivo, in a dosage-dependent manner. Constitutively active mutants are hypermorphic as they trigger proliferation and death more potently than their wild-type counterparts. Moreover, SFK-induced proliferation and apoptosis are largely independent events, as blocking ectopic proliferation does not block cell death. Further, DCsk (the Drosophila homolog of the C-terminal Src kinase) phosphorylates and interacts genetically with the wild-type SFKs, but not with the constitutively active mutants in which a conserved C-terminal tyrosine was mutated to phenylalanine, providing the first in vivo evidence that Csk regulates SFKs during development through phosphorylation of their C-terminal tyrosine.
- Published
- 2004
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