CGC Bibliography Paper 5255

Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling.

Bruinsma JJ, Jirakulaporn T, Muslin AJ, Kornfeld K

Medline:

Citation:

Developmental Cell 2: 567-578 2002

Type:

ARTICLE

Genes:

cdf-1 let-23 let-60 lin-1 lin-12 lin-15

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 Zn2+ efflux and reducing the concentration of cytosolic Zn2+, and cytosolic Zn2+ negatively regulates Ras-mediated signaling. Physiological concentrations of Zn2+ cause a significant inhibition of Ras-mediated signaling. These findings suggest that Zn2+ negatively regulates a conserved element of the signaling pathway and that Zn2+ regulation is important for maintaining the inactive state of the Ras pathway.