THE KSR-1 GENE ENCODES A NOVEL PROTEIN-KINASE INVOLVED IN RAS-MEDIATED SIGNALING IN C-ELEGANS

By screening for mutations that suppress the vulval defects caused by a constitutively active let gb ras gene, we identified six loss-of-function alleles of ksr-1, a novel C. elegans gene. Our genetic analysis showed ksr-1 positively mediates Ras signaling and functions downstream of or in parallel to let-60. In the absence of ksr-1 function, normal Ras signaling is impaired only slightly, suggesting ksr-1 may act to modulate, or in a branch that diverges from, the main signaling pathway. The predicted KSR-1 protein has a protein kinase domain and is most similar to a recently identified Drosophila protein involved in Ras signaling. We propose that the function of ksr-1 is evolutionarily conserved.