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

We have developed an efficient expression cloning system that allows rapid isolation of complementary DNAs able to induce the transformed phenotype. We searched for molecules expressed in epithelial cells and possessing transforming potential to fibroblasts, and cloned a cDNA for the normal receptor...

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Bibliographic Details
Published in:	Nature (London) 1993-04, Vol.362 (6419), p.462-465
Main Authors:	MIKI, T, SMITH, C. L, LONG, J. E, EVA, A, FLEMING, T. P
Format:	Article
Language:	eng
Subjects:	3T3 Cells Amino Acid Sequence Animals Base Sequence bcr Biological and medical sciences cDNA Cell Line, Transformed Cell physiology Cell transformation Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes CNDA Deoxyribonucleic acid DNA DNA - genetics DNA - isolation & purification ect2 Ect2 protein Fundamental and applied biological sciences. Psychology G proteins Gene Library gene products genes Genetics GTP-Binding Proteins - genetics guanine nucleotide-binding protein homology Identification and classification Keratinocytes - physiology Kinetics Mice Mice, Inbred Strains Molecular and cellular biology Molecular Sequence Data NIM 3T3 cells nucleotide sequence Oligodeoxyribonucleotides Oncogenes predictions Proteins Proto-Oncogene Proteins - biosynthesis Proto-Oncogene Proteins - genetics Restriction Mapping Retroviridae Proteins, Oncogenic - genetics Sequence Homology, Amino Acid Transfection transformation
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Summary:	We have developed an efficient expression cloning system that allows rapid isolation of complementary DNAs able to induce the transformed phenotype. We searched for molecules expressed in epithelial cells and possessing transforming potential to fibroblasts, and cloned a cDNA for the normal receptor of a growth factor secreted by NIH/3T3 cells. 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 oncogene. Each of these genes encodes regulatory molecules or effectors for Rho-like small GTP-binding proteins. 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.
ISSN:	0028-0836 1476-4687