The Drosophila Son of sevenless (Sos) gene functions in the signaling pathway initiated by the Sevenless receptor tyrosine kinase. It encodes the Drosophila homologue of CDC25, an activator of Ras in the yeast Saccharomyces cerevisiae. Two widely expressed mammalian homologues of Sos (mSos) have now been identified and characterized. They encode for 150-kD proteins that are Ras-specific guanine nucleotide exchange factors. Genetic and biochemical studies indicate that Sos proteins bind directly to the SH2- and SH3-domain-containing adaptor protein GRB2/Drk. This interaction defines a pathway by which receptor tyrosine kinases can communicate with Ras.