{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:17:24Z","timestamp":1785867444538,"version":"3.56.0"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["2020R1A2C2010321"],"award-info":[{"award-number":["2020R1A2C2010321"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["RS-2023-00237729"],"award-info":[{"award-number":["RS-2023-00237729"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["A423100"],"award-info":[{"award-number":["A423100"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["KGM55022423"],"award-info":[{"award-number":["KGM55022423"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea Basic Science Institute grant","award":["2020R1A2C2010321"],"award-info":[{"award-number":["2020R1A2C2010321"]}]},{"name":"Korea Basic Science Institute grant","award":["RS-2023-00237729"],"award-info":[{"award-number":["RS-2023-00237729"]}]},{"name":"Korea Basic Science Institute grant","award":["A423100"],"award-info":[{"award-number":["A423100"]}]},{"name":"Korea Basic Science Institute grant","award":["KGM55022423"],"award-info":[{"award-number":["KGM55022423"]}]},{"name":"KRIBB Research Initiative Program","award":["2020R1A2C2010321"],"award-info":[{"award-number":["2020R1A2C2010321"]}]},{"name":"KRIBB Research Initiative Program","award":["RS-2023-00237729"],"award-info":[{"award-number":["RS-2023-00237729"]}]},{"name":"KRIBB Research Initiative Program","award":["A423100"],"award-info":[{"award-number":["A423100"]}]},{"name":"KRIBB Research Initiative Program","award":["KGM55022423"],"award-info":[{"award-number":["KGM55022423"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays a critical role in regulating the activity of Rho guanosine triphosphatases (GTPases). Phosphorylation of RhoGDI1 dynamically modulates the activation of Rho GTPases, influencing cell proliferation and migration. This study explored the involvement of Never In Mitosis A (NIMA)-related serine\/threonine protein kinase 2 (NEK2) in phosphorylating RhoGDI1 and its implications in cancer cell behavior associated with tumor progression. We employed GST pull-down assays and immunoprecipitation to investigate the interaction between NEK2 and RhoGDI1. Truncation fragments identified the region of RhoGDI1 responsible for binding with NEK2. Phosphorylation assays determined the site of NEK2-mediated phosphorylation on RhoGDI1. Functional assays were conducted using overexpression of the RhoGDI1 substitution mutant to assess their impact on cancer cell behavior. NEK2 directly bound to RhoGDI1 and phosphorylated it at Ser174. This phosphorylation event facilitated cancer cell proliferation and motility by activating RhoA and Rac1. The RhoGDI1 aa 112\u2013134 region was critical for the binding to NEK2. Disruption of the NEK2\u2013RhoGDI1 interaction through overexpression of a RhoGDI1 truncated fragment (aa 112\u2013134) led to diminished RhoGDI1 phosphorylation and RhoA\/Rac1 activation induced by NEK2, resulting in reduced cancer cell proliferation and migration. Moreover, in vivo studies showed reduced tumor growth and lung metastasis when the NEK2\u2013RhoGDI1 interaction was disrupted. This study indicates that NEK2 promotes the metastatic behaviors of cancer cells by activating RhoA and Rac1 by phosphorylating RhoGDI1.<\/jats:p>","DOI":"10.3390\/cells13242072","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T06:48:39Z","timestamp":1734331719000},"page":"2072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["NEK2 Phosphorylates RhoGDI1 to Promote Cell Proliferation, Migration and Invasion Through the Activation of RhoA and Rac1 in Colon Cancer Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Jeewon","family":"Lim","sequence":"first","affiliation":[{"name":"Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"},{"name":"Department of Biomolecular Science, University of Science and Technology (UST), Daejeon 34113, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yo-Sep","family":"Hwang","sequence":"additional","affiliation":[{"name":"Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyang-Ran","family":"Yoon","sequence":"additional","affiliation":[{"name":"Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Min","family":"Park","sequence":"additional","affiliation":[{"name":"Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahyeong","family":"Han","sequence":"additional","affiliation":[{"name":"Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"},{"name":"Department of Biomolecular Science, University of Science and Technology (UST), Daejeon 34113, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9489-0283","authenticated-orcid":false,"given":"Taeho","family":"Kwon","sequence":"additional","affiliation":[{"name":"Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56216, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28644, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2273-9677","authenticated-orcid":false,"given":"Hee-Jun","family":"Cho","sequence":"additional","affiliation":[{"name":"Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"},{"name":"Department of Biomolecular Science, University of Science and Technology (UST), Daejeon 34113, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Gu","family":"Lee","sequence":"additional","affiliation":[{"name":"Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"},{"name":"Department of Biomolecular Science, University of Science and Technology (UST), Daejeon 34113, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/nrm2476","article-title":"Mammalian Rho GTPases: New insights into their functions from in vivo studies","volume":"9","author":"Heasman","year":"2008","journal-title":"Nat. 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