Sci. STKE, 9 October 2001
Reactive Oxygen Species ROS Inhibits MAPK Signaling
The effect of genetic mutations that can alter cellular redox state-affected signaling through the receptor tyrosine kinase to Ras to mitogen-activated protein kinase (MAPK) pathway can be studied in vivo by analyzing genetic interactions in the Drosophila eye and wing. Selenoproteins are characterized by the presence of selenocysteine and are involved in controlling the cellular levels of reactive oxygen species (ROS). Moery et al. studied how mutations in a key enzyme in the biosynthesis of selenoproteins, selenophosphate synthetase (sps1), affected MAPK signaling stimulated by the Sevenless (Sev) receptor in the eye and the Drosophila epidermal growth factor receptor (DER) in the wing. Loss of the sps1 gene suppresses the rough eye phenotype caused by activated forms of the kinases Sev, Raf, and MAPK, but does not suppress the rough eye phenotype associated with the activated guanosine triphosphatase Ras. In the wing, loss of sps1 in combination with activated DER or Raf restored wild-type vein formation. Increasing cellular ROS by expression of a mutant catalase gene also suppressed the activated MAPK signaling, supporting the interpretation that the Ras to MAPK pathway is inhibited by ROS in vivo. The regulation by ROS appeared to be specific for the Ras-MAPK pathway because no change in phenotype was observed with activated insulin, Notch, Wnt, or DPP (a Drosophila transforming growth factor-β receptor pathway). The authors point out that these results differ from those obtained in cultured cells and suggest that the prolonged elevation in ROS in the Drosophila mutants may have a different effect than the acute elevations in ROS in the cultured cell experiments.
M. Morey, F. Serras, J. Baguñà, E. Hafen , M. Corominas, Modulation of the Ras/MAPK signalling pathway by the redox function of selenoproteins in Drosophila melanogaster. Dev. Biol. 238, 145-156 (2001). [Online Journal]
Citation: ROS Inhibits MAPK Signaling. Sci. STKE 2001, tw371 (2001).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882