Cell, Vol. 94, 119-130, July 10, 1998
We describe the identification and characterization of a novel gene,
sur-8, that positively regulates Ras-mediated signal transduction during
C.
elegans vulval development. Reduction of sur-8 function suppresses
an activated ras mutation and dramatically enhances phenotypes of mpk-1
MAP kinase and ksr-1 mutations, while increase of sur-8 dosage enhances
an activated ras mutation. sur-8 appears to act downstream of or in
parallel to ras but upstream of raf. sur-8 encodes a conserved protein
that is composed predominantly of leucine-rich repeats. The SUR-8 protein
interacts directly with Ras but not with the Ras(P34G) mutant protein,
suggesting that SUR-8 may mediate its effects through Ras binding. A structural
and functional SUR-8 homolog in humans specifically binds K-Ras and
N-Ras but not H-Ras in vitro.