{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:15:06Z","timestamp":1791335706284,"version":"4.3.1"},"reference-count":73,"publisher":"National Academy of Sciences","issue":"1","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM144237"],"award-info":[{"award-number":["GM144237"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011820","name":"MOE | Saudi Arabian Cultural Mission","doi-asserted-by":"publisher","award":["1007758160"],"award-info":[{"award-number":["1007758160"]}],"id":[{"id":"10.13039\/501100011820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:p>\n                    Induction of cell fates by growth factors impacts many facets of developmental biology and disease. LIN-3\/EGF induces the equipotent vulval precursor cells (VPCs) in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    to assume the 3\u02da\u22123\u02da\u22122\u02da\u22121\u02da\u22122\u02da\u22123\u02da pattern of cell fates. 1\u02da and 2\u02da cells become specialized epithelia and undergo stereotyped series of cell divisions to form the vulva. Conversely, 3\u02da cells are relatively quiescent and nonspecialized; they divide once and fuse with the surrounding epithelium. 3\u02da cells have thus been characterized as passive, uninduced, or ground state. Based on our previous studies, we hypothesized that a 3\u02da-promoting program would confer resistance to cell fate-transformation by inappropriately activated 1\u02da and 2\u02da fate-promoting LET-60\/Ras and LIN-12\/Notch, respectively. Deficient MIG-15\/CNH-MAP4 Kinase meets the expectations of genetic interactions for a 3\u02da-promoting protein. Moreover, endogenous MIG-15 is required for expression of a fluorescent biomarker of 3\u02da cell fate, is expressed in VPCs, and functions cell autonomously in VPCs. The Ras family small GTPase RAP-2, orthologs of which activate orthologs of MIG-15 in other systems, emulates these functions of MIG-15. However, gain of RAP-2 function has no effect on patterning, suggesting its activity is constitutive in VPCs. The 3\u02da biomarker is expressed independently of the AC, raising questions about the cellular origin of 3\u02da-promoting activity. Activated LET-60\/Ras and LIN-12\/Notch repress expression of the 3\u02da biomarker, suggesting that the 3\u02da-promoting program is both antagonized by as well as antagonizes 1\u02da- and 2\u02da- promoting programs. This study provides insight into developmental properties of cells historically considered to be nonresponding to growth factor signals.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2414321121","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T13:42:02Z","timestamp":1735652522000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["RAP-2 and CNH-MAP4 Kinase MIG-15 confer resistance in bystander epithelium to cell-fate transformation by excess Ras or Notch activity"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3511-2665","authenticated-orcid":false,"given":"Razan A.","family":"Fakieh","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, School of Medicine, Texas A&M Health Science Center, Texas A&M University","place":["Houston"]},{"name":"Clinical Laboratory Sciences Department, College of Applied 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