TY - JOUR
T1 - C. elegans ksr-1 and ksr-2 have both unique and redundant functions and are required for MPK-1 ERK phosphorylation
AU - Ohmachi, Mitsue
AU - Rocheleau, Christian E.
AU - Church, Diane
AU - Lambie, Eric
AU - Schedl, Tim
AU - Sundaram, Meera V.
N1 - Funding Information:
We thank Y. Kohara for cDNA clones; J. Kimble, S. Kim, and the Caenorhabditis Genetics Center for strains; and members of our laboratories for helpful discussions and comments on the manuscript. This work was supported by National Institutes of Health grants GM49785 (to E.L.), GM63310 (to T.S.), and GM58540 (to M.V.S.). C.E.R. is a postdoctoral fellow of the Jane Coffin Childs Memorial Fund for Medical Research.
PY - 2002/3/5
Y1 - 2002/3/5
N2 - 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 [1]. 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 [2, 3]. 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.
AB - 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 [1]. 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 [2, 3]. 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.
UR - http://www.scopus.com/inward/record.url?scp=0037022533&partnerID=8YFLogxK
U2 - 10.1016/S0960-9822(02)00690-5
DO - 10.1016/S0960-9822(02)00690-5
M3 - Article
C2 - 11882296
AN - SCOPUS:0037022533
SN - 0960-9822
VL - 12
SP - 427
EP - 433
JO - Current Biology
JF - Current Biology
IS - 5
ER -