Ral GEF With PH Domain And SH3 Binding Motif 2 (RALGPS2)

RALGPS2 is a potential candidate gene for susceptibility to Alzheimer disease linked to 1q24. Guanine nucleotide exchange factors (GEFs) are responsible for coupling cell surface receptors to Ras protein activation.These molecules share the core catalytic domain of other Ras family GEFs but lack the catalytic non-conserved domain that is believed to contribute to Sos1 integrity. In vitro binding and in vivo nucleotide exchange assays indicate that these GEFs specifically catalyze the GTP loading of the Ral GTPase when overexpressed in 293T cells. A central proline-rich motif associated with the Src homology (SH)2/SH3-containing adapter proteins Grb2 and Nck in vivo, whereas a pleckstrin homology (PH) domain was located at the GEF C terminus.