title: SP600125 induces Src and type I IGF receptor phosphorylation independent of JNK.
abstract: c-Jun N-terminal kinases (JNK) are members of the mitogen-activated protein kinase (MAPK) family that have important roles in signal transduction. The small molecule SP600125 is widely used in biochemical studies as a JNK inhibitor. However, recent studies indicate that SP600125 may also act independent of JNK. Here, we report that SP600125 can induce Src, type I insulin-like growth factor receptor (IGF-IR), Akt and Erk1/2 phosphorylation. Notably, these effects are independent of its inhibition of JNK. Inhibition of Src abrogates the stimulation of IGF-IR, Akt and Erk1/2 phosphorylation. IGF-IR knockdown blunts the induction of both Akt and Erk1/2 phosphorylation by SP600125. Moreover, combination of SP600125 and the Src inhibitor saracatinib synergistically inhibits cell proliferation. We conclude that SP600125 can activate Src-IGF-IR-Akt/Erk1/2 signaling pathways independent of JNK.
authors.affiliation: State Key Laboratory of Biotherapy, Section of Oncogene, West China Hospital, Sichuan University, Chengdu 610041, China. kongqingbincdut@163.com.
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu 610041, China. hui_hua@scu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Hua
authors.affiliation: State Key Laboratory of Biotherapy, Section of Oncogene, West China Hospital, Sichuan University, Chengdu 610041, China. cuianguo1618@126.com.
authors.forename: Anguo
authors.initials: A
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Biotherapy, Section of Oncogene, West China Hospital, Sichuan University, Chengdu 610041, China. shaoting89410@126.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Shao
authors.affiliation: State Key Laboratory of Biotherapy, Section of Oncogene, West China Hospital, Sichuan University, Chengdu 610041, China. lanringsong@163.com.
authors.forename: Peiying
authors.initials: P
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biotherapy, Section of Oncogene, West China Hospital, Sichuan University, Chengdu 610041, China. jyangfu@scu.edu.cn.
authors.forename: Yangfu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000873:Anthracenes / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D034741:RNA, Small Interfering; C432165:pyrazolanthrone; D017526:Receptor, IGF Type 1; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3