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sli-1, a negative regulator of let-23-mediated signaling in C. elegans

Jongeward, Gregg D. and Clandinin, Thomas R. and Sternberg, Paul W. (1995) sli-1, a negative regulator of let-23-mediated signaling in C. elegans. Genetics, 139 (4). pp. 1553-1566. ISSN 0016-6731. PMCID PMC1206484.

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By screening for suppressors of hypomorphic mutations of let-23, a receptor tyrosine kinase necessary for vulval induction in Caenorhabditis elegans, we recovered > or = 12 mutations defining the sli-1 (suppressor of lineage defect) locus. sli-1 mutations suppress four of five phenotypes associated with hypomorphic alleles of let-23 but do not suppress let-23 null alleles. Thus, a sli-1 mutation does not bypass the requirement for functional let-23 but rather allows more potent LET-23-dependent signaling. Mutations at the sli-1 locus are otherwise silent with respect to vulval differentiation and cause only a low-penetrance abnormal head phenotype. Mutations at sli-1 also suppress the vulval defects but not other defects associated with mutations of sem-5, whose product likely interacts with LET-23 protein during vulval induction. Mutations at sli-1 suppress lin-2, lin-7 and lin-10 mutations but only partially suppress lin-3 and let-60 mutations and do not suppress a lin-45 mutation. The sli-1 locus displays dosage sensitivity: severe reduction of function alleles of sli-1 are semidominant suppressors; a duplication of the sli-1(+) region enhances the vulvaless phenotype of hypomorphic mutations of let-23. We propose that sli-1 is a negative regulator that acts at or near the LET-23-mediated step of the vulval induction pathway. Our analysis suggests that let-23 can activate distinct signaling pathways in different tissues: one pathway is required for vulval induction; another pathway is involved in hermaphrodite fertility and is not regulated by sli-1.

Item Type:Article
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URLURL TypeDescription CentralArticle
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 1995 by the Genetics Society of America. Manuscript received August 30, 1994; Accepted for publication December 19, 1994. We are grateful to Gladys Medina for superb media preparation. We thank Andy Golden, Junho Lee, Bino Palmer, and other members of our laboratory for comments on the manuscript. Supported by U.S. Public Health Service grant HD-23690 to P.W.S., an investigator of the Howard Hughes Medical Institute. T.R.C. was supported in part by an Amgen Fund Fellowship. Some strains were supplied by the Caenorhabditis Genetics Center.
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC1206484
Record Number:CaltechAUTHORS:20190515-110430955
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Official Citation:sli-1, a negative regulator of let-23-mediated signaling in C. elegans. G D Jongeward, T R Clandinin and P W Sternberg. GENETICS April 1, 1995 vol. 139 no. 4 1553-1566
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95511
Deposited By: Tony Diaz
Deposited On:16 May 2019 02:43
Last Modified:03 Oct 2019 21:14

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