Oncogene ect2 is related to regulators of small GTP-binding proteins

Abstract

WE have developed an efficient expression cloning system that allows rapid isolation of complementary DNAs able to induce the transformed phenotype^{1, 2}. We searched for molecules expressed in epithelial cells and possessing transforming potential to fibro-blasts, and cloned a cDNA for the normal receptor of a growth factor secreted by NIH/3T3 cells^{3, 4}. Here we report a second novel transforming gene, ect2. The isolated cDNA is activated by amino-terminal truncation of the normal product. The Ect2 protein has sequence similarity within a central core of 255 amino acids with the products of the breakpoint cluster gene, bcr (ref. 5), the yeast cell cycle gene, CDC24 (ref. 6), and the dbl oncogene⁷. Each of these genes encodes regulatory molecules or effectors for Rho-like small GTP-binding proteins^8–10. The baculovirus-expressed Ect2 protein could bind highly specifically to Rho and Rac proteins, whereas the dbl product showed broader binding specificity to Rho family proteins. Thus ect2 is a new member of an expanding family, whose products have transforming properties and interact with Rho-like proteins of the Ras superfamily.