{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T22:33:56Z","timestamp":1768084436099,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T00:00:00Z","timestamp":1366070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>TMEM67 mutations are associated with severe autosomal recessive polycystic kidney disease (ARPKD) in both humans and animals. However, the molecular mechanisms underlying the pathogenesis of PKD caused by TMEM67 mutations remain to be determined. We have investigated the possible signalling pathways involved in the pathogenesis of PKD. Overexpression of TMEM67 in human embryonic kidney (HEK293) cells triggered the activation of overall tyrosine phosphorylated proteins, extracellular signal\u2010regulated kinase (ERK) and c\u2010jun N\u2010terminal KINASE (JNK). Activation was suppressed by pharmacological inhibitors of ERK or JNK. Activation of the mammalian target of rapamycin (mTOR) or p70s kinase (S6K) did not occur, although elevated phosphorylation of eIF4E\u2010binding protein 1 (4E\u2010BP1), a target of S6K, was seen. In animal studies, activation of a variety of signalling molecules was linked to ERK, JNK and 4E\u2010BP1. Significant induction of phosphorylation of tyrosine phosphorylated proteins, ERK and 4E\u2010BP1, at different postnatal ages was detected in mutant kidneys of B6C3Fe a\/a\u2010<jats:italic>bpck<\/jats:italic> mice, a cystic renal disease mouse model caused by TMEM67 loss of function mutation. Based on these in vitro and in vivo observations, we propose that TMEM67 mutations cause PKD through ERK\u2010 and JNK\u2010dependent signalling pathways, which may provide novel insight into the therapy of polycystic kidney diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbin.10081","type":"journal-article","created":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T09:54:05Z","timestamp":1375782845000},"page":"694-702","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evidence that <scp>TMEM<\/scp>67 causes polycystic kidney disease through activation of <scp>JNK<\/scp>\/<scp>ERK<\/scp>\u2010dependent pathways"],"prefix":"10.1002","volume":"37","author":[{"given":"E","family":"Du","sequence":"first","affiliation":[{"name":"Tianjin Institute of Urology The Second Hospital of Tianjin Medical University Tianjin 300211 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomical Sciences and Neurobiology School of Medicine, University of Louisville Louisville, Kentucky 40292 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunying","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Medicine School of Medicine, University of Louisville Louisville, Kentucky 40292 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Anatomical Sciences and Neurobiology School of Medicine, University of Louisville Louisville, Kentucky 40292 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengsheng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Anatomical Sciences and Neurobiology School of Medicine, University of Louisville Louisville, Kentucky 40292 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruifa","family":"Han","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Urology The Second Hospital of Tianjin Medical University Tianjin 300211 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,4,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/510499"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000314380"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251194298"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.99"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008040412"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.043794"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.29.18623"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfn744"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110367200"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2011.06.003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10497"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.8.4947"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.97"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.15.4404"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.21.2385"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2008.40.6.699"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00755.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf361"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805890200"},{"key":"e_1_2_9_21_1","first-page":"577","article-title":"Novel role of c\u2010jun N\u2010terminal kinase in regulating the initiation of cap\u2010dependent translation","volume":"40","author":"Patel MR","year":"2012","journal-title":"Int J Oncol"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/353670a0"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410697200"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204825"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509694103"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1713"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.4.1538-1548.2006"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00023.x"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcbin.10081","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.10081","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T13:32:35Z","timestamp":1697635955000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.10081"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,16]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1002\/cbin.10081"],"URL":"https:\/\/doi.org\/10.1002\/cbin.10081","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"value":"1065-6995","type":"print"},{"value":"1095-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,16]]},"assertion":[{"value":"2012-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-02-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}