The catalytic domain of the mouse sos1 gene product activates Ras proteins in vivo and in vitro.

Nucleotide exchange factors (NEFs) which are structurally related to the yeast Saccharomyces cerevisiae CDC25 gene product have recently been identified in mammals. One of these NEFs, cdc25, has been shown to activate RAS in yeast and to promote nucleotide exchange on RAS proteins in vitro. The cdc25 from mammals is expressed at high levels in brain tissue but not in a variety of other tissues examined. The vertebrate sos1 and sos2 gene products have a domain structurally related to the catalytic domain of the yeast CDC25NEF. The expression pattern of sos1 and sos2 is widespread, showing detectable levels of expression in all tissues examined, although the levels vary dramatically in various tissues. In this report we demonstrate that the catalytic domain of SOS1NEF can complement the loss of CDC25 function in yeast, can bind tightly to the nucleotide-free form of H-ras in vitro and can promote nucleotide exchange on the H-ras protein in vitro.