Superoxide inhibits guanine nucleotide exchange factor (GEF) action on Ras, but not on Rho, through desensitization of Ras to GEF.

ABSTRACT: Ras and Rho GTPases are molecular switches for various vital cellular signaling pathways. Overactivation of these GTPases often causes development of cancer. Guanine nucleotide exchange factors (GEFs) and oxidants function to upregulate these GTPases through facilitation of guanine nucleotide exchange (GNE) of these GTPases. However, the effect of oxidants on GEF functions, or vice versa, has not been known. We show that, via targeting Ras Cys(51), an oxidant inhibits the catalytic action of Cdc25-the catalytic domain of RasGEFs-on Ras. However, the enhancement of Ras GNE by an oxidant continues regardless of the presence of Cdc25. Limiting RasGEF action by an oxidant may function to prevent the pathophysiological overactivation of Ras in the presence of both RasGEFs and oxidants. The cont

SUBMITTER: Wey M 

PROVIDER: S-EPMC4327825 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature