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Mol Cell Biol, August 1998, p. 4556-4564, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Caenorhabditis elegans SUR-5, a Novel but Conserved
Protein, Negatively Regulates LET-60 Ras Activity during
Vulval Induction
Trent
Gu,1
Satoshi
Orita,1 2 and
Min
Han1 *
Howard Hughes Medical Institute, Department
of Molecular, Cellular and Developmental Biology, University of
Colorado, Boulder, Colorado 80309-0347,1 and
Shionogi Institute for Medical Science, and Settsu-shi,
Osaka 566, Japan2
Received 4 March 1998/Returned for modification 13 April
1998/Accepted 11 May 1998
The let-60 ras gene acts in a signal transduction
pathway to control vulval differentiation in Caenorhabditis
elegans. By screening suppressors of a dominant negative
let-60 ras allele, we isolated three loss-of-function
mutations in the sur-5 gene which appear to act as negative
regulators of let-60 ras during vulval induction.
sur-5 mutations do not cause an obvious mutant phenotype of
their own, and they appear to specifically suppress only one
of the two groups of let-60 ras dominant negative
mutations, suggesting that the gene may be involved in a specific
aspect of Ras activation. Consistent with its negative function,
overexpressing sur-5 from an extragenic array
partially suppresses the Multivulva phenotype of an activated
let-60 ras mutation and causes synergistic phenotypes with a lin-45 raf mutation. We have cloned
sur-5 and shown that it encodes a novel protein.
We have also identified a potential mammalian SUR-5 homolog that is
about 35% identical to the worm protein. SUR-5 also has some sequence
similarity to acetyl coenzyme A synthetases and is predicted to contain
ATP/GTP and AMP binding sites. Our results suggest that
sur-5 gene function may be conserved through evolution.
*
Corresponding author. Mailing address: Howard Hughes
Medical Institute, Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309-0347. Phone: (303) 492-2261. Fax: (303) 735-0175. E-mail:
mhan{at}colorado.edu.

Present address: Promega Corp., Madison, WI 53711-5399.
Mol Cell Biol, August 1998, p. 4556-4564, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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