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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 dagger 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.

dagger 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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