Characterization, expression and chromosomal localization of a human gene homologous to the mouse Lsc oncogene, with strongest expression in hematopoetic tissues

Abstract

A human cDNA clone, denoted sub1.5, was isolated from cDNA library generated from human T cells. The sub1.5 cDNA sequence was novel and was not identical to any known cDNA sequences in the GenBank. Recently, however, a mouse cDNA (Lsc) with high homology to sub1.5 was identified, indicating that the sub1.5 sequence may represent the human homologue of the mouse Lsc gene. The sub1.5 cDNA includes an open reading frame of 875 amino acids, predicting a protein with molecular weight of 97 kDa. Like Lsc, sub1.5 shows homology to the previous described oncogene Lbc, in particular to two functional domains in the Lbc protein; the Dbl proto-oncogene homology domain and the pleckstrin homology domain. Lsc is proposed to be an oncogene and is a member of a growing family of proteins that may function as activators of the Rho family GTPases. Members of the Rho family regulates the polymerization of actin to produce stress fibers. Activation of Rho GTPases by sub1.5 is also indicated by our studies, as stress fiber formation is observed in serum-starved stable NIH3T3 sub1.5 transfectants. Sub1.5 cDNA hybridizes to two major transcripts of 3.5 and 5 kb size and the strongest expression is seen in hematopoietic tissues like thymus, lymph nodes, peripheral blood leukocytes and spleen. We also show that both purified B and T cells express sub1.5. In addition, our data indicate that sub1.5 mRNA is abundantly expressed in CD34⁺ human progenitor cells. Fluorescent in situ hybridisation, using sub1.5 cDNA as a probe on human metaphases, shows that the sub1.5 gene is localized to chromosome 19q13.13.