Ras promotes cell survival by antagonizing both JNK and Hid signals in the Drosophila eye

BMC Dev Biol. 2009 Oct 20:9:53. doi: 10.1186/1471-213X-9-53.

Abstract

Background: Programmed cell death, or apoptosis, is a fundamental physiological process during normal development or in pathological conditions. The activation of apoptosis can be elicited by numerous signalling pathways. Ras is known to mediate anti-apoptotic signals by inhibiting Hid activity in the Drosophila eye. Here we report the isolation of a new loss-of-function ras allele, rasKP, which causes excessive apoptosis in the Drosophila eye.

Results: This new function is likely to be mediated through the JNK pathway since the inhibition of JNK signalling can significantly suppress rasKP-induced apoptosis, whereas the removal of hid only weakly suppresses the phenotype. Furthermore, the reduction of JNK signalling together with the expression of the baculovirus caspase inhibitor p35, which blocks Hid activity, strongly suppresses the rasKP cell death. In addition, we find a strong correlation between rasKP-induced apoptosis in the eye disc and the activation of JNK signalling.

Conclusion: In the Drosophila eye, Ras may protect cells from apoptosis by inhibiting both JNK and Hid activities. Surprisingly, reducing Ras activity in the wing, however, does not cause apoptosis but rather affects cell and organ size. Thus, in addition to its requirement for cell viability, Ras appears to mediate different biological roles depending on the developmental context and on the level of its expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Cell Survival / genetics
  • Cell Survival / physiology*
  • Drosophila / cytology
  • Drosophila / embryology
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • Eye / cytology
  • Eye / embryology
  • Eye / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Viral Proteins / genetics
  • Viral Proteins / physiology
  • Wings, Animal / cytology
  • Wings, Animal / embryology
  • Wings, Animal / metabolism
  • ras Proteins / genetics
  • ras Proteins / physiology*

Substances

  • Drosophila Proteins
  • HID protein, Drosophila
  • Neuropeptides
  • Viral Proteins
  • p35 protein, Baculovirus
  • JNK Mitogen-Activated Protein Kinases
  • ras Proteins