{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:25:51Z","timestamp":1781702751788,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,5,18]],"date-time":"2009-05-18T00:00:00Z","timestamp":1242604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The spatio\u2010temporal regulation of hepatocyte proliferation is a critical issue in liver regeneration. Here, in normal and regenerating liver as well as in developing liver, we examined its expression\/localization of IQGAP3, which was most recently reported as a Ras\/Rac\/Cdc42\u2010binding proliferation factor associated with cell\u2013cell contacts in epithelial\u2010type cells. In parallel, the expression\/localization of Rac\/Cdc42\u2010binding IQGAP1\/2 was examined. IQGAP3 showed a specific expression in proliferating hepatocytes positive for the proliferating marker Ki\u201067, the levels of expressions of mRNAs and proteins were significantly increased in hepatocytes in liver regeneration and development. In immunofluorescence, IQGAP3 was highly enriched at cell\u2013cell contacts of hepatocytes. IQGAP1 and IQGAP2 were exclusively expressed in Kupffer and sinusoidal endothelial cells, respectively, in normal, regenerating, and developing liver. The expression of IQGAP1, but not of IQGAP2, was increased in CCl<jats:sub>4<\/jats:sub>\u2010induced (but not in partial hepatectomy\u2010induced) liver regeneration. Exclusive expression\/localization of IQGAP3 to hepatocytes in the liver likely reflects the specific involvement of the IQGAP3\/Ras\/ERK signaling cascade in hepatocyte proliferation in addition to the previously identified signaling pathways, possibly by integrating cell\u2013cell contact\u2010related proliferating signaling events. On the other hand, the Rac\/Cdc42\u2010binding properties of IQGAP1\/2\/3 may be related to the distinct modes of remodeling due to the different strategies which induced proliferation of liver cells; partial hepatectomy, CCl<jats:sub>4<\/jats:sub>injury, or embryonic development. Thus, the functional orchestration of Ras and the Ras homologous (Rho) family proteins Rac\/Cdc42 likely plays a critical role in liver regeneration and development. J. Cell. Physiol. 220: 621\u2013631, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21798","type":"journal-article","created":{"date-parts":[[2009,5,18]],"date-time":"2009-05-18T17:47:11Z","timestamp":1242668831000},"page":"621-631","source":"Crossref","is-referenced-by-count":28,"title":["Involvement of IQGAP3, a regulator of Ras\/ERK\u2010related cascade, in hepatocyte proliferation in mouse liver regeneration and development"],"prefix":"10.1002","volume":"220","author":[{"given":"Koshi","family":"Kunimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Nojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikazu","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Okanoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Tsukita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,5,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1996.0316"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7401089"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200612071"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"4568","DOI":"10.1182\/blood.V87.11.4568.bloodjournal87114568","article-title":"Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans","volume":"87","author":"Couvelard A","year":"1996","journal-title":"Blood"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1993.1069"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M500393-MCP200"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"71S","DOI":"10.1016\/S0031-6997(25)06797-3","article-title":"Mechanisms of cell injury with hepatotoxic chemicals","volume":"36","author":"Farber JL","year":"1984","journal-title":"Pharmacol Rev"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80412-2"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20969"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21551"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260307"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01324802"},{"key":"e_1_2_6_14_1","first-page":"186","article-title":"Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal","volume":"12","author":"Higgins GM","year":"1931","journal-title":"Arch Pathol"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-12-1215"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e08-07-0691"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2004.08.004"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.2.697-701.2000"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21172"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.60"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1757"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02379"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1175"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2007.03.003"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.22.8035-8043.2002"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01090-07"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100380170119"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.9.6003"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03356"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209525"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20691"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.21798","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.21798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T13:59:54Z","timestamp":1739109594000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.21798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5,18]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,9]]}},"alternative-id":["10.1002\/jcp.21798"],"URL":"https:\/\/doi.org\/10.1002\/jcp.21798","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,5,18]]}}}