TableEdit

Ohmachi, M, Rocheleau, CE, Church, D, Lambie, E, Schedl, T and Sundaram, MV (2002) C. elegans ksr-1 and ksr-2 have both unique and redundant functions and are required for MPK-1 ERK phosphorylation. Curr. Biol. 12:427-33

Kinase Suppressor of Ras (KSR) is a conserved protein that positively regulates Ras signaling and may function as a scaffold for Raf, MEK, and ERK. However, the precise role of KSR is not well understood, and some observations have suggested that KSR might act in a parallel pathway. In C. elegans, ksr-1 is only required for a specific Ras-mediated process (sex myoblast migration) and is a nonessential positive regulator of other Ras-mediated developmental events. We report the existence of a second C. elegans ksr gene, ksr-2, which is required for Ras-mediated signaling during germline meiotic progression and functions redundantly with ksr-1 during development of the excretory system, hermaphrodite vulva, and male spicules. Thus, while the ksr-1 and ksr-2 genes are individually required only for specific Ras-dependent processes, together these two genes appear necessary for most aspects of Ras-mediated signaling in C. elegans. The finding that ksr-2; ksr-1 double mutants have strong ras-like phenotypes and severely reduced or absent levels of diphosphorylated MPK-1 ERK strongly supports models where KSR acts to promote the activation or maintenance of the Raf/MEK/ERK kinase cascade.

PubMed

Amino Acid Sequence; Animals; Base Sequence; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; DNA, Helminth/genetics; Female; Genes, Helminth; Male; Mitogen-Activated Protein Kinase 1; Molecular Sequence Data; Mutation; Phenotype; Phosphorylation; Protein Kinases/genetics; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/metabolism; Sequence Homology, Amino Acid; Signal Transduction