Drosophila Src-family kinases function with Csk to regulate cell proliferation and apoptosis

Oncogene. 2004 Jun 10;23(27):4754-62. doi: 10.1038/sj.onc.1207635.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • CSK Tyrosine-Protein Kinase
  • Cell Division / genetics*
  • Cell Division / physiology
  • Cloning, Molecular
  • Drosophila / enzymology
  • Drosophila / genetics*
  • Drosophila Proteins / metabolism*
  • Enzyme Activation
  • Eye / embryology
  • Eye / ultrastructure
  • Glutathione Transferase / metabolism
  • Larva
  • Membrane Proteins / metabolism*
  • Microscopy, Electron, Scanning
  • Mutation
  • Phosphoproteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • src-Family Kinases / metabolism*


  • Drosophila Proteins
  • Membrane Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Glutathione Transferase
  • CSK Tyrosine-Protein Kinase
  • Csk protein, Drosophila
  • src-Family Kinases