Identification of a novel mouse Dbl proto-oncogene splice variant: evidence that SEC14 domain is involved in GEF activity regulation

Abstract

The Rho guanine nucleotide exchange factor protoDbl is involved in different biochemical pathways affecting cell proliferation and migration. The N-terminal sequence of protoDbl contains negative regulatory elements that restrict the catalytic activity of the DH-PH module. Here, we report the identification of a new mouse protoDbl splice variant lacking exon 3. We found that the splice variant mRNA is expressed in the spleen and bone marrow lymphocytes, adrenal gland, gonads and brain. The protoDbl variant protein was detectable in the brain. The newly identified variant displays the disruption of the SEC14 domain, positioned on exons 2 and 3 in the protoDbl N-terminal region. We show here that an altered SEC14 sequence leads to enhanced Dbl translocation to the plasma membrane and to augmented transforming and exchange activity.

Keywords: 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride; AEBSF; Alternative splicing; CRAL; Cellular Retinaldehyde domain; DH; Dbl; Dbl homology; Diffuse Large B cell Lymphoma; GAPDH; GEF; Glyceraldehyde 3-phosphate dehydrogenase; Guanine nucleotide exchange factor; PAK-CRIB; PH; Pleckstrin homology; Rho GTPases; SEC14 protein domain; SEC14p; Saccaromyces cerevisiae phosphatidylinositol transfer protein domain; TRIO; Transforming activity; Triple functional domain; p21-Activated Kinase-Cdc42/Rac Interactive Binding; protoDbl oncogene.