{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T08:35:15Z","timestamp":1776242115330,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1998,8,1]],"date-time":"1998-08-01T00:00:00Z","timestamp":901929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Genetic analysis of lin-1 loss-of-function mutations suggests that lin-1 controls multiple cell-fate decisions during Caenorhabditis elegans development and is negatively regulated by a conserved receptor tyrosine kinase-Ras-ERK mitogen-activated protein (MAP) kinase signal transduction pathway. LIN-1 protein contains an ETS domain and presumably regulates transcription. We identified and characterized six gain-of-function mutations that define a new class of lin-1 allele. These lin-1 alleles appeared to be constitutively active and unresponsive to negative regulation. Each allele has a single-base change that affects the predicted C terminus of LIN-1, suggesting this region is required for negative regulation. The C terminus of LIN-1 was a high-affinity substrate for Erk2 in vitro, suggesting that LIN-1 is directly regulated by ERK MAP kinase. Because mpk-1 ERK MAP kinase controls at least one cell-fate decision that does not require lin-1, our results suggest that MPK-1 contributes to the specificity of this receptor tyrosine kinase-Ras-MAP kinase signal transduction pathway by phosphorylating different proteins in different developmental contexts. These lin-1 mutations all affect a four-amino-acid motif, FQFP, that is conserved in vertebrate and Drosophila ETS proteins that are also phosphorylated by ERK MAP kinase. This sequence may be a substrate recognition motif for the ERK subfamily of MAP kinases.<\/jats:p>","DOI":"10.1093\/genetics\/149.4.1809","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T01:59:21Z","timestamp":1619575161000},"page":"1809-1822","source":"Crossref","is-referenced-by-count":89,"title":["Gain-of-Function Mutations in the Caenorhabditis elegans lin-1 ETS Gene Identify a C-Terminal Regulatory Domain Phosphorylated by ERK MAP Kinase"],"prefix":"10.1093","volume":"149","author":[{"given":"Dave","family":"Jacobs","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg J","family":"Beitel","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott G","family":"Clark","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H Robert","family":"Horvitz","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry","family":"Kornfeld","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1998,8,1]]},"reference":[{"key":"2022010310425041800_R1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0076-6879(95)55031-3","article-title":"Assay and expression of mitogen-activated protein kinase, MAP kinase kinase, and Raf","volume":"255","author":"Alessi","year":"1995","journal-title":"Methods Enzymol."},{"key":"2022010310425041800_R2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/348503a0","article-title":"Caenorhabditis elegans ras gene let-60 acts as a switch in the pathway of vulval induction","volume":"348","author":"Beitel","year":"1990","journal-title":"Nature"},{"key":"2022010310425041800_R3","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1101\/gad.9.24.3149","article-title":"The Caenorhabditis elegans gene lin-1 encodes an ETS-domain protein and defines a branch of the vulval induction pathway","volume":"9","author":"Beitel","year":"1995","journal-title":"Genes Dev."},{"key":"2022010310425041800_R4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","article-title":"The genetics of Caenorhabditis elegans","volume":"77","author":"Brenner","year":"1974","journal-title":"Genetics"},{"key":"2022010310425041800_R5","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/370386a0","article-title":"The ETS domain protein Pointed-P2 is a target of MAP kinase in the Sevenless signal transduction pathway","volume":"370","author":"Brunner","year":"1994","journal-title":"Nature"},{"key":"2022010310425041800_R6","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1242\/dev.121.8.2525","article-title":"Three genes of the MAP kinase cascade, mek-2, mpk-1\/sur-1 and let-60 ras, are required for meiotic cell cycle progression in Caenorhabditis elegans","volume":"121","author":"Church","year":"1995","journal-title":"Development"},{"key":"2022010310425041800_R7","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/356340a0","article-title":"C. elegans cell-signaling gene sem-5 encodes a protein with SH2 and SH3 domains","volume":"356","author":"Clark","year":"1992","journal-title":"Nature"},{"key":"2022010310425041800_R8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0092-8674(93)90293-Y","article-title":"Control of cellfates in the central body region of C. elegans by the homeobox gene lin-39","volume":"74","author":"Clark","year":"1993","journal-title":"Cell"},{"key":"2022010310425041800_R9","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/0022-2836(77)90059-6","article-title":"Genetic studies of the lac repressor. 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