title: C. elegans ksr-1 and ksr-2 have both unique and redundant functions and are required for MPK-1 ERK phosphorylation.
abstract: 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.
authors.affiliation: Department of Genetics, Washington University School of Medicine, 63110, St. Louis, MO, USA
authors.forename: Mitsue
authors.initials: M
authors.lastname: Ohmachi
authors.forename: Christian E
authors.initials: CE
authors.lastname: Rocheleau
authors.forename: Diane
authors.initials: D
authors.lastname: Church
authors.forename: Eric
authors.initials: E
authors.lastname: Lambie
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
authors.forename: Meera V
authors.initials: MV
authors.lastname: Sundaram
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018509:DNA, Helminth / Q000235:genetics; D005260:Female; D017238:Genes, Helminth; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; C460981:ksr-2 protein, C elegans; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans