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

• Mouse protoDbl oncogene displays a splicing form lacking exon 3.
• The first consequence of a missing exon 3 is a disrupted SEC14 protein domain.
• Altered SEC14 sequence leads to enhanced Dbl translocation to the plasma membrane.
• Altered SEC14 sequence leads to augmented Dbl transforming and exchange activity.
• ProtoDbl variant protein is expressed in the brain.

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.