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By the use of specific inhibitors, RNA interference, and coimmunoprecipitation, we show that PCV2 induces autophagy in PK-15 cells through a pathway involving the kinases AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase 1\/2 (ERK1\/2), the tumor suppressor protein TSC2, and the mammalian target of rapamycin (mTOR). AMPK and ERK1\/2 positively regulate autophagy through negative control of the mTOR pathway by phosphorylating TSC2 in PCV2-infected PK-15 cells. Thus, PCV2 might induce autophagy via the AMPK\/ERK\/TSC2\/mTOR signaling pathway in the host cells, representing a pivotal mechanism for PCV2 pathogenesis.<\/jats:p>","DOI":"10.1128\/jvi.01434-12","type":"journal-article","created":{"date-parts":[[2012,8,23]],"date-time":"2012-08-23T00:17:20Z","timestamp":1345681040000},"page":"12003-12012","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["Porcine Circovirus Type 2 Induces Autophagy via the AMPK\/ERK\/TSC2\/mTOR Signaling Pathway in PK-15 Cells"],"prefix":"10.1128","volume":"86","author":[{"given":"Binglin","family":"Zhu","sequence":"first","affiliation":[{"name":"Zhejiang University Institute of Preventive Veterinary Medicine, Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, and Key Laboratory of Molecular Animal Nutrition of the Ministry of Education, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingshan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Zhejiang University Institute of Preventive Veterinary Medicine, Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, and Key Laboratory of Molecular Animal Nutrition of the Ministry of Education, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang University Institute of Preventive Veterinary Medicine, Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, and Key Laboratory of Molecular Animal Nutrition of the Ministry of Education, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangbing","family":"Shuai","sequence":"additional","affiliation":[{"name":"Zhejiang Entry-Exit Inspection and Quarantine Bureau, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Li","sequence":"additional","affiliation":[{"name":"Zhejiang University Institute of Preventive Veterinary Medicine, Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, and Key Laboratory of Molecular Animal Nutrition of the Ministry of Education, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihuan","family":"Fang","sequence":"additional","affiliation":[{"name":"Zhejiang University Institute of Preventive Veterinary Medicine, Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, and Key Laboratory of Molecular Animal Nutrition of the Ministry of Education, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409143102"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2011.09.041"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/104063870101300301"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.2.2.2458"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07366.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5184"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201152200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2011.11.008"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(03)00079-5"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.3424"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1199104"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6555"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.4248"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1196371"},{"key":"e_1_3_2_16_2","first-page":"33","article-title":"Macroautophagy signaling and regulation","volume":"335","author":"Esclatine A","year":"2009","unstructured":"EsclatineA ChaumorcelM CodognoP. 2009. 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