SOS and guanine nucleotide exchange factors

SOS (Son of Sevenless, since it was first isolated in a genetic screen of the Sevenless receptor tyrosine kinase pathway in Drosophila) is a guanine nucleotide exchange factor that catalyses the exchange of GDP for GTP on Ras. Since GTP-Ras is active, SOS is an agonist of Ras function. SOS binds Grb-2 via a polyproline region/SH3 domain interaction and can be found complexed with this adapter in the cytoplasm of resting cells. Upon cellular stimulation of receptor tyrosine kinases, the Grb-2-SOS complex is recruited to the tyrosine phosphorylated receptor (via the SH2 domain of Grb-2) allowing interaction between SOS and Ras, which is membrane localised via an acylated C-terminal domain. Membrane targetted SOS mutants constitutively activate Ras.