Editors' ChoiceRedox Regulation

c-K-Ras and c-H-Ras Antagonism

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Science's STKE  24 Apr 2001:
Vol. 2001, Issue 79, pp. tw5
DOI: 10.1126/stke.2001.79.tw5

The c-K-Ras and c-H-Ras are nearly identical in sequence except for their twenty COOH-terminal amino acid residues. Santillo et al. showed that c-K-Ras and c-H-Ras could regulate the amounts of reactive oxygen species (ROS) in cells transfected with either ras gene. Overexpression of c-H-Ras in cells led to increased amounts of ROS, whereas c-K-Ras overexpression diminished the amounts of ROS, by increasing the activity of superoxide dismutase (SOD) (a ROS scavenger), in a mitogen-activated protein kinase (MAPK)-dependent manner. Mutation of a stretch of lysine residues at the c-K-Ras COOH-terminus (not present in c-H-Ras) blocked MAPK-dependent activation of SOD, but did not affect MAPK-dependent transcription. However, mutation of the farnesylation CAAX box at the COOH-terminus of c-K-Ras did not perturb SOD activation, but did block MAPK-dependent transcription, suggesting that plasma localization of c-K-Ras (which requires the intact CAAX box), is not important for c-K-Ras- and MAPK-dependent SOD activation. c-K-Ras but not c-H-Ras can also localize to the surface of mitochondria. The authors suggest that this subpopulation of c-K-Ras might be important for SOD activation.

M. Santillo, P. Mondola, R. Serù, T. Annella, S. Cassano, I. Ciullo, M. F. Tecce, G. Iacomino, S. Damiano, G Cuda, R. Paternò, V. Martignetti, E. Mele, A. Feliciello, E. V. Avvedimento, Opposing functions of Ki- and Ha-ras genes in the regulation of redox signals. Curr. Biol. 11, 614-619 (2001). [Online Journal]

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