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Modulation of KSR activity in Caenorhabd ... R-1 kinase and PP2A phosphatase
Modulation of KSR activity in Caenorhabditis elegans by Zn ions, PAR-1 kinase and PP2A phosphatase.
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Vulval differentiation in Caenorhabditis elegans is controlled by a conserved signal transduction pathway mediated by Ras and a kinase cascade that includes Raf, Mek and MAPK. Activation of this cascade is positively regulated by a number of proteins such as KSR (kinase suppressor of Ras), SUR-8/SOC-2, SUR-6/PP2A-B and CDF-1. We describe the functional characterization of sur-7 and several genes that regulate signaling downstream of ras. We identified sur-7 by isolating a mutation that suppresses an activated ras allele, and showed that SUR-7 is a divergent member of the cation diffusion facilitator family of heavy metal ion transporters that is probably localized to the endoplosmic recticulum membrane and regulates cellular Zn(2+) concentrations. Genetic double mutant analyses suggest that the SUR-7-mediated effect is not a general toxic response. Instead, Zn(2+) ions target a specific step of the pathway, probably regulation of the scaffolding protein KSR. Biochemical analysis in mammalian cells indicates that high Zn(2+) concentration causes a dramatic increase of KSR phosphorylation. Genetic analysis also indicates that PP2A phosphatase and PAR-1 kinase act downstream of Raf to positively and negatively regulate KSR activity, respectively.
Yoder JH, Chong H, Guan KL, Han M
The EMBO journal
2004-01-14 00:00
23
1
111-9
Alleles,Amino Acid Sequence,Animals,Caenorhabditis elegans,Caenorhabditis elegans Proteins,Consensus Sequence,Embryonic Induction,Endoplasmic Reticulum,Female,Genes, Helminth,Models, Biological,Molecular Sequence Data,Mutation,Phosphoprotein Phosphatase,Phosphorylation,Protein Structure, Tertiary,Protein-Serine-Threonine Kinases,Proto-Oncogene Proteins c-raf,RNA Interference,Recombinant Proteins,Sequence Homology, Amino Acid,Signal Transduction,Vulva,Zinc,ras Proteins,Caenorhabditis elegans Proteins,Recombinant Proteins,SUR-7 protein, C elegans,Zinc,PAR-1 protein, C elegans,Protein-Serine-Threonine Kinases,Proto-Oncogene Proteins c-raf,Phosphoprotein Phosphatase,ras Proteins
Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institution, University of Colorado, Boulder, CO, USA
EMBO J.
0261-4189
10.1038/sj.emboj.7600025
7600025
498
True
14685271
