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Papers In Press, published online ahead of print November 27, 2002
Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas, Madrid 28029
Corresponding Author: pcrespo{at}harle.iib.uam.es
Ras GTPases include the isoforms H-Ras, K-Ras and N-Ras. Despite their great biochemical and biological similarities, evidence is mounting suggesting that Ras proteins may not be functionally redundant. A widespread strategy for studying small GTPases is the utilization of dominant inhibitory mutants that specifically block the activation of their respective wild-type proteins. As such, H-Ras N17 has proved to be extremely valuable as a tool to probe Ras functions. However, a comparative study on the inhibitory specificities of H-, K- and N-Ras N17 mutants has not been approached thus far. Herein, we demonstrate that H-, K- and N-Ras N17 mutants exhibit markedly distinct inhibitory effects towards H-, K-, and N-Ras. H-Ras N17 can effectively inhibit the activation of all three isoforms. K-Ras N17 completely blocks the activation of K-Ras and is only slightly inhibitory on H-Ras. And N-Ras N17 can mainly inhibit N-Ras activation. In light of the recent data on the compartmentalization of H-Ras and K-Ras in the plasma membrane, here we present for the first time a description of N-Ras cellular microlocalization. Overall, our results on Ras N17 mutants specificities exhibit a marked correlation with the localization of the Ras isoforms to distinct membrane microdomains
J. Biol. Chem, 10.1074/jbc.M209807200
Submitted on September 24, 2002
Revised on November 19, 2002
Accepted on November 27, 2002
Differences on the inhibitory specificities of H-Ras, K-Ras and N-Ras (N17) dominant negative mutants are related to their membrane microlocalization
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