Exploring the Many Facets of Sos Mediated Signaling. S. Silver , F. Chen , I. Rebay. Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142-2142.

   In Drosophila as well as in mammalian systems, Son-of-sevenless (Sos) has been characterized as an important component of Receptor Tyrosine Kinase signaling due to its function as a guanine nucleotide exchange factor (GEF) for Ras. Sos also has a GEF exchange domain for Rho-family GTPases, which has been shown in mammalian cells to be specific for Rac. Thus, Sos may function to mediate crosstalk between Ras and Rho-family mediated signaling events.
In a screen for dominant enhancers of sev-Yan^act, a complementation group of eleven alleles (EY2-3) was isolated and mapped to the Sos locus. Interestingly, Sos^null alleles do not enhance sev-Yan^act. Also, in genetic interaction assays with sev-Ras^V12, Sos^null alleles suppress the phenotype, while Sos^EY2-3 alleles do not. Sequencing of four Sos^EY2-3 alleles indicates that these may be hypomorphs that interfere specifically with RasGEF activity. Tissue culture experiments to measure GEF activities of wildtype and mutant Sos protein will provide insight as to the mechanism of Sos mediated activation of Ras as compared to Rac. The choice of small GTPase may be influenced by conditions such as intracellular localization, binding specificity, or the presence or absence of cofactors.