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Comments on Jacobs D et al. (1997) International C. elegans Meeting "GAIN-OF-FUNCTION MUTATIONS SUGGEST LIN-1 IS NEGATIVELY REGULATED BY MAP KINASE PHOSPHORYLATION" (0)
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Jacobs D, Beitel GJ, Horvitz HR, & Kornfeld K (1997). GAIN-OF-FUNCTION MUTATIONS SUGGEST LIN-1 IS NEGATIVELY REGULATED BY MAP KINASE PHOSPHORYLATION presented in International C. elegans Meeting. Unpublished information; cite only with author permission.
lin-1(lf) mutations cause a highly expressive multivulva phenotype suggesting lin-1 is an important negative regulator of the 1! vulval cell fate. Genes in the ras signaling pathway promote the 1! fate, and epistasis analyses suggest lin-1 functions downstream of these genes, including mpk-1 MAP kinase, suggesting lin-1 is negatively regulated by the action of this signaling pathway. The predicted LIN-1 protein contains an N-terminal ets domain, suggesting LIN-1 may be a DNA-binding transcription factor. We identified four different lin-1 mutations that cause partially penetrant larval lethality characterized by a rod-like morphology and vulval defects typical of a lack of vulval induction. These same phenotypes are caused by loss-of-function mutations in genes in the ras signaling pathway but are the opposite of the phenotypes caused by a loss-of-function mutation in lin-1. Dosage studies suggest that these four lin-1 alleles are gain-of-function mutations. We determined the base changes present in these alleles, and each is predicted to affect the C-terminal region of LIN-1. This region appears to be highly divergent from but nonetheless similar to regions of vertebrate ets domain-containing proteins that are phosphorylated and thereby regulated by MAP kinase. These observations suggest that the C-terminus of LIN-1 is phosphorylated by MAP kinase, that this phosphorylation negatively regulates the activity of LIN-1, and that the mutant LIN-1 proteins have lost the ability to be phosphorylated and thereby negatively regulated but retain the ability to inhibit the 1! vulval cell fate. We are currently testing these biochemical hypotheses.
Affiliation:
- Department of Molecular Biology and Pharmacology, Washington U. Medical School, St. Louis, MO 63110 USA HHMI, Dept. Biology, MIT, Cambridge, MA 02139, USA