sur-6 encodes a PR55 regulatory subunit of the heterotrimeric PP2A phosphatase that positively regulates Ras signaling during vulval precursor cell fate specification and acts between Ras and Raf . The two missense mutants upon which this analysis was based cause a low percent Vul phenotype and no other phenotypes. However RNAi analysis indicates that
sur-6 has a role in embryonic development. We have obtained a deletion allele
sur-6(
sv30),from Simon Tuck's Lab (Umea Univ), which deletes 5 of its 6 WD40 repeats.
sv30 mutants are maternal effect embryonic lethal and are more Vul than the other alleles, but not as severely Vul as mutants in the main Ras/Raf/MAPK pathway. The genetic interactions of
sur-6(
sv30) with other regulators of the Ras pathway are similar to those seen with the missense alleles. Hence there appears to be no absolute requirement for SUR-6 in modulation of the Ras pathway and the missense alleles affect the Ras signaling functions of
sur-6 more severely than its other functions. In other systems PR55/SUR-6 can either inhibit or promote the catalytic activity of PP2A. The Kohara and Baillie labs have shown that
let-92 encodes the catalytic subunit of PP2A. We have shown that
let-92 also acts positively in the context of vulval development. This implies that SUR-6 promotes of the catalytic activity of PP2A which positively regulates the Ras/MAPK cascade, perhaps by removing inhibitory phosphates from a substrate such as LIN-45 Raf or KSR-1. The ser/thr kinases AKT, SGK and C-TAK1/PAR-1 have been identified biochemically as candidate inhibitory kinases that act on RAF or KSR to down-regulate the Ras/Raf/ MAPK cascade in mammalian tissue culture cells. Using RNAi in sensitized genetic backgrounds we have found no evidence so far that AKT and SGK have a role in vulval development. However we find that
par-1(
b274lf)/par-1
(zu310ts) trans-heterozygotes are weakly Muv. Additionally we find that
par-1(lf) reverts the suppressed (non-Muv) phenotype of
sur-6(
ku123);
let-60(
n1046gf) and
let-60(
n1046gf);
ksr-1(
n2526) double mutants. By contrast,
par-1(lf) does not reduce the ability of
lin-45(
ku112) to suppress the
let-60gf Muv phenotype. Therefore
par-1 has an inhibitory role in vulval development. We are currently investigating the relationship between PP2A and PAR-1 in vulval development.