EXPRESSION CLONING OF LSC, A NOVEL ONCOGENE WITH STRUCTURAL SIMILARITIES TO THE DBL FAMILY OF GUANINE-NUCLEOTIDE EXCHANGE FACTORS

Citation
Ip. Whitehead et al., EXPRESSION CLONING OF LSC, A NOVEL ONCOGENE WITH STRUCTURAL SIMILARITIES TO THE DBL FAMILY OF GUANINE-NUCLEOTIDE EXCHANGE FACTORS, The Journal of biological chemistry, 271(31), 1996, pp. 18643-18650
Citations number
72
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
271
Issue
31
Year of publication
1996
Pages
18643 - 18650
Database
ISI
SICI code
0021-9258(1996)271:31<18643:ECOLAN>2.0.ZU;2-X
Abstract
In a screen for genes with oncogenic potential expressed by the murine B6SUtA(1) myeloid progenitor cell line, we isolated a 2.5-kilobase pa ir cDNA whose expression causes strong morphological transformation an d deregulated proliferation of NIH 3T3 cells. The transforming cDNA en codes a truncated protein (designated Lsc) with a region of sequence s imilarity to the product of the lbc oncogene. This region includes the tandem Dbl homology and pleckstrin homology domains that are hallmark s of the Dbl-like proteins, a family of presumptive or demonstrated gu anine nucleotide exchange factors that act on Rho family GTPases. Lsc requires intact Dbl homology and pleckstrin homology domains for its o ncogenic activity. The transforming activity of Lsc in NIH 3T3 cells i s reduced by cotransfection with p190 (a GTPase activating protein for Rho family GTPases) and the Rho family dominant-negative mutants RhoA (19N), CDC42(17N), and Racl(17N), These results indicate a role for th e Rho family of GTPases in mediating the transforming activity of Lsc and are consistent with the exchange specificities that have been attr ibuted to Dbl family members. The Ise gene is expressed in a variety o f tissues and is particularly abundant in hemopoietic tissues (thymus, spleen, and bone marrow). Lsc is a member of a growing family of prot eins that may function as activators of Rho family GTPases in a develo pmental or tissue-specific manner.