<p>Small GTPases of the Ras family alternate between 2 conformations induced by the binding of either GTP or GDP. Ras family proteins are active in the GTP-bound conformation and inactive in the GDP-bound conformation. Guanine nucleotide exchange factors (GEFs) induce the dissociation of GDP to allow association of the more abundant GTP, and as such act as positive regulators of the Ras family.</p> <p>In quiescent cells, Ras is predominantly GDP bound and inactive. Growth factor stimulation promotes the conversion of Ras-GDP to Ras-GTP through a reaction that is catalyzed by GEFs. The activation of Ras in response to growth factor binding to receptor tyrosine kinases (RTKs) is dependent on the Son of sevenless (Sos) GEF. Sos was originally identified in <taxon tax_id="7227">Drosophila melanogaster</taxon> by its ability to couple the sevenless RTK to Ras. Sos is conserved across eukaryotes. This entry consists of proteins from species ranging from <taxon tax_id="44689">Dictyostelium discoideum</taxon> (Slime mold) to <taxon tax_id="9606">Homo sapiens</taxon> (Human).</p> <p>The catalytic domain of Sos spans a central region of approximately 450 amino acids. This domain is necessary and sufficient to catalyze guanine nucleotide exchange on Ras and displays sequence similarity to the catalytic domain of the <taxon tax_id="4932">Saccharomyces cerevisiae</taxon> Ras exchanger CDC25. The N terminus of Sos contains a Dbl Homology (DH) domain followed by a Pleckstrin Homology (PH) domain connected by linker segment DH domains, which are invariably followed by PH domains, function as exchange factors for members of the Rho family of GTPases. The C-terminal region of Sos contains multiple proline rich sequences and phosphorylation sites. The proline rich sequences mediate interactions with multiple Src homology 3 (SH3) domain containing proteins [<cite idref="PUB00034793"/>].</p>