{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:34:53Z","timestamp":1774067693908,"version":"3.50.1"},"reference-count":83,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T00:00:00Z","timestamp":1589414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A6A1A03015642"],"award-info":[{"award-number":["2017R1A6A1A03015642"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In this study, we investigated the functional role of isoprenylcysteine carboxyl methyltransferase (ICMT) and its methylatable substrate Ras in Toll-like receptor (TLR)-activated macrophages and in mouse inflammatory disease conditions. ICMT and RAS expressions were strongly increased in macrophages under the activation conditions of TLRs by lipopolysaccharide (LPS, a TLR4 ligand), pam3CSK (TLR2), or poly(I:C) (TLR3) and in the colons, stomachs, and livers of mice with colitis, gastritis, and hepatitis. The inhibition and activation of ICMT and Ras through genetic and pharmacological approaches significantly affected the activation of interleukin-1 receptor-associated kinase (IRAK)s, tumor necrosis factor receptor associated factor 6 (TRAF6), transforming growth factor-\u03b2-activated kinase 1 (TAK1), mitogen-activated protein kinase (MAPK), and MAPK kinases (MAPKKs); translocation of the AP-1 family; and the expressions of inflammation-related genes that depend on both MyD88 and TRIF. Interestingly, the Ras\/ICMT-mediated inflammatory reaction critically depends on the TIR domains of myeloid differentiation primary response 88 (MyD88) and TIR-domain-containing adapter-inducing interferon-\u03b2 (TRIF). Taken together, these results suggest that ICMT and its methylated Ras play important roles in the regulation of inflammatory responses through cooperation with the TIR domain of adaptor molecules.<\/jats:p>","DOI":"10.3390\/cells9051216","type":"journal-article","created":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T10:27:19Z","timestamp":1589452039000},"page":"1216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Isoprenylcysteine Carboxyl Methyltransferase and Its Substrate Ras Are Critical Players Regulating TLR-Mediated Inflammatory Responses"],"prefix":"10.3390","volume":"9","author":[{"given":"Woo Seok","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-9801","authenticated-orcid":false,"given":"Han Gyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-5310","authenticated-orcid":false,"given":"Eunji","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Yun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7696-1025","authenticated-orcid":false,"given":"Nur","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7166-3659","authenticated-orcid":false,"given":"Young-Su","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Life Science, Kyonggi University, Suwon 16227, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunggyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Research and Business Foundation, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunmi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Kwangwoon University, Seoul 01897, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7937-0167","authenticated-orcid":false,"given":"Byong Chul","family":"Yoo","sequence":"additional","affiliation":[{"name":"Division of Translational Science, Research Institute, National Cancer Center, Goyang 10408, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeung-Whan","family":"Han","sequence":"additional","affiliation":[{"name":"Research Center for Epigenome Regulation, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narayanan","family":"Parameswaran","sequence":"additional","affiliation":[{"name":"Department of Physiology and Division of Pathology, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7881-9599","authenticated-orcid":false,"given":"Ji Hye","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-9927","authenticated-orcid":false,"given":"Jae Youl","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/90609","article-title":"Toll-like receptors: Critical proteins linking innate and acquired immunity","volume":"2","author":"Akira","year":"2001","journal-title":"Nat. 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