{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T11:16:16Z","timestamp":1782472576515,"version":"3.54.5"},"reference-count":44,"publisher":"The Company of Biologists","issue":"16","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":2583,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:p>The group I members of the Nm23 (non-metastatic) gene family encode nucleoside diphosphate kinases (NDPKs) that have been implicated in the regulation of cell migration, proliferation and differentiation. Despite their developmental and medical significance, the molecular functions of these NDPKs remain ill defined. To minimize confounding effects of functional compensation between closely related Nm23 family members, we studied ndk-1, the sole Caenorhabditis elegans ortholog of group I NDPKs, and focused on its role in Ras\/mitogen-activated protein kinase (MAPK)-mediated signaling events during development. ndk-1 inactivation leads to a protruding vulva phenotype and affects vulval cell fate specification through the Ras\/MAPK cascade. ndk-1 mutant worms show severe reduction of activated, diphosphorylated MAPK in somatic tissues, indicative of compromised Ras\/MAPK signaling. A genetic epistasis analysis using the vulval induction system revealed that NDK-1 acts downstream of LIN-45\/Raf, but upstream of MPK-1\/MAPK, at the level of the kinase suppressors of ras (KSR-1\/2). KSR proteins act as scaffolds facilitating Ras signaling events by tethering signaling components, and we suggest that NDK-1 modulates KSR activity through direct physical interaction. Our study reveals that C. elegans NDK-1\/Nm23 influences differentiation by enhancing the level of Ras\/MAPK signaling. These results might help to better understand how dysregulated Nm23 in humans contributes to tumorigenesis.<\/jats:p>","DOI":"10.1242\/dev.094011","type":"journal-article","created":{"date-parts":[[2013,7,30]],"date-time":"2013-07-30T13:07:12Z","timestamp":1375189632000},"page":"3486-3495","source":"Crossref","is-referenced-by-count":34,"title":["The NM23-H1\/H2 homolog NDK-1 is required for full activation of Ras signaling in<i>C. elegans<\/i>"],"prefix":"10.1242","volume":"140","author":[{"given":"Neda","family":"Masoudi","sequence":"first","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter stny. 1\/C, H-1117 Budapest, Hungary."},{"name":"Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dow Street, Dundee DD1 5EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Fancsalszky","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter stny. 1\/C, H-1117 Budapest, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Pourkarimi","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter stny. 1\/C, H-1117 Budapest, Hungary."},{"name":"Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dow Street, Dundee DD1 5EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Vellai","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter stny. 1\/C, H-1117 Budapest, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Alexa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter stny. 1\/C, H-1117 Budapest, Hungary."},{"name":"Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Pusztaszeri \u00fat 59-67, H-1025 Budapest, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Rem\u00e9nyi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter stny. 1\/C, H-1117 Budapest, Hungary."},{"name":"Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Pusztaszeri \u00fat 59-67, H-1025 Budapest, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Gartner","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dow Street, Dundee DD1 5EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Mehta","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, Centre for CVS and Lung Biology, Ninewells Hospital Medical School, Dundee DD1 9SY, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"Tak\u00e1cs-Vellai","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter stny. 1\/C, H-1117 Budapest, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042622110193100_R1","doi-asserted-by":"crossref","first-page":"3545","DOI":"10.1242\/dev.068148","article-title":"Notch and Ras promote sequential steps of excretory tube development in C. elegans","volume":"138","author":"Abdus-Saboor","year":"2011","journal-title":"Development"},{"key":"2021042622110193100_R2","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00210-011-0645-7","article-title":"Correlation of NM23-H1 cytoplasmic expression with metastatic stage in human prostate cancer tissue","volume":"384","author":"Andolfo","year":"2011","journal-title":"Naunyn Schmiedebergs Arch. 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