The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2-1p36.3.

Guanine nucleotide exchange factors from the Dbl family are proto-oncogenic proteins that activate small GTPases of the Rho family. Here we report the characterization of GEF720, a novel Dbl-like protein related to p115Rho-GE F. GEF720 activated RhoA both in our recently developed Yeast Exchange Assa y and in biochemical in vitro exchange assays. GEF720 induced RhoA dependen t assembly of actin stress fibers in REF52 fibroblastic cells. In NIH3T3 ce lls this Dbl-like protein elicited formation of transformation foci with a morphology similar to RhoA-V14 induced foci. In the PC12 neuron-like cell l ine, expression of GEF720, whose mRNA is brain specific, inhibited NGF-indu ced neurite outgrowth. Finally, GEF720 gene is located on human chromosome 1 on band 1p36, between Tumor Protein 73 and Tumor Necrosis Factor Receptor 12, two genes rearranged in many neuroblastoma cell lines. Together, these results show that this new Dbl related protein, GEF720, is an exchange fac tor that can directly activate RhoA in vivo and is potentially involved in the control of neuronal cell differentiation. GEF720 is also a new candidat e gene involved in the progression of neuroblastoma and developmental abnor malities associated with rearrangements in the 1p36 chromosomal region.