IN-VIVO FUNCTIONAL-ANALYSIS OF THE RAS EXCHANGE FACTOR SON OF SEVENLESS

The Son of sevenless (Sos) protein functions as a guanine nucleotide t ransfer factor for Ras and interacts with the receptor tyrosine kinase Sevenless through the protein Drk, a homolog of mammalian Grb2. In vi vo structure-function analysis revealed that the amino terminus of Sos was essential for its function in flies. A molecule lacking the amino terminus was a potent dominant negative. In contrast, a Sos fragment lacking the Drk binding sites was functional and its activity was depe ndent on the presence of the Sevenless receptor. Furthermore, membrane localization of Sos was independent of Drk. A possible role for Drk a s an activator of Sos is discussed and a Drk-independent interaction b etween Sos and Sevenless is proposed that is likely mediated by the pl eckstrin homology domain within the amino terminus.