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(Received for publication, November 16, 1995, and in revised form, March 29, 1996)
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From the In a screen for genes with oncogenic potential
expressed by the murine B6SUtA1 myeloid progenitor cell
line, we isolated a 2.5-kilobase pair cDNA whose expression causes
strong morphological transformation and deregulated proliferation of
NIH 3T3 cells. The transforming cDNA encodes a truncated protein
(designated Lsc) with a region of sequence similarity to the product of
the lbc oncogene. This region includes the tandem Dbl
homology and pleckstrin homology domains that are hallmarks of the
Dbl-like proteins, a family of presumptive or demonstrated guanine
nucleotide exchange factors that act on Rho family GTPases. Lsc
requires intact Dbl homology and pleckstrin homology domains for its
oncogenic activity. The transforming activity of Lsc in NIH 3T3 cells
is 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 Rac1(17N). These results indicate a role for
the Rho family of GTPases in mediating the transforming activity of Lsc
and are consistent with the exchange specificities that have been
attributed to Dbl family members. The lsc gene is expressed
in a variety of tissues and is particularly abundant in hemopoietic
tissues (thymus, spleen, and bone marrow). Lsc is a member of a growing
family of proteins that may function as activators of Rho family
GTPases in a developmental or tissue-specific manner.
Department of Medical
Genetics, University of British Columbia, Vancouver, British Columbia
V6T 1Z1, Canada and 
Terry Fox Laboratory, British
Columbia Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada
and the ¶ Curriculum in Genetics and Molecular Biology and
'' Department of Pharmacology and the Lineberger Comprehensive
Cancer Center, University of North Carolina,
Chapel Hill, North Carolina 27599
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