Caenorhabditis elegans SUR-5, a Novel but Conserved Protein, Negatively Regulates LET-60 Ras Activity during Vulval Induction

Thelet-60 ras gene acts in a signal transduction pathway to control vulval differentiation inCaenorhabditis elegans . By screening suppressors of a dominant negativelet-60 ras allele, we isolated three loss-of-function mutations in thesur-5 gene which appear to act as negative regulators oflet-60 ras during vulval induction.sur-5 mutations do not cause an obvious mutant phenotype of their own, and they appear to specifically suppress only one of the two groups oflet-60 ras dominant negative mutations, suggesting that the gene may be involved in a specific aspect of Ras activation. Consistent with its negative function, overexpressingsur-5 from an extragenic array partially suppresses the Multivulva phenotype of an activatedlet-60 ras mutation and causes synergistic phenotypes with alin-45 raf mutation. We have clonedsur-5 and shown that it encodes a novel protein. We have also identified a potential mammalian SUR-5 homolog that is about 35% identical to the worm protein. SUR-5 also has some sequence similarity to acetyl coenzyme A synthetases and is predicted to contain ATP/GTP and AMP binding sites. Our results suggest thatsur-5 gene function may be conserved through evolution.