title: Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling.
abstract: C. elegans cdf-1 was identified in a genetic screen for regulators of Ras-mediated signaling. CDF-1 is a cation diffusion facilitator protein that is structurally and functionally similar to vertebrate ZnT-1. These proteins have an evolutionarily conserved function as positive regulators of the Ras pathway, and the Ras pathway has an evolutionarily conserved ability to respond to CDF proteins. CDF proteins regulate Ras-mediated signaling by promoting Zn(2+) efflux and reducing the concentration of cytosolic Zn(2+), and cytosolic Zn(2+) negatively regulates Ras-mediated signaling. Physiological concentrations of Zn(2+) cause a significant inhibition of Ras-mediated signaling. These findings suggest that Zn(2+) negatively regulates a conserved element of the signaling pathway and that Zn(2+) regulation is important for maintaining the inactive state of the Ras pathway.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Janelle J
authors.initials: JJ
authors.lastname: Bruinsma
authors.forename: Tanawat
authors.initials: T
authors.lastname: Jirakulaporn
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Muslin
authors.forename: Kerry
authors.initials: K
authors.lastname: Kornfeld
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D005260:Female; D015870:Gene Expression; D017136:Ion Transport; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D014844:Vulva / Q000254:growth & development; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C456542:cdf-1 protein, C elegans; D018631:ras Proteins; D015032:Zinc