title: Dual specificity phosphotase 18, interacting with SAPK, dephosphorylates SAPK and inhibits SAPK/JNK signal pathway in vivo.
abstract: The SAPK/JNKs play important roles in numerous cellular processes, and for this reason they have become putative drug targets. Most dual-specificity protein phosphatases (DSPs) play important roles in the regulation of mitogenic signal transduction and cell cycle control in response to extracellular stimuli. Dual-specificity phosphatase 18 (DUSP18), a newly recognized SAPK/JNK phosphatase, is widely expressed. This expression is modulated in response to extracellular stimuli. By phosphorylation assay, pull down and coimmunoprecipitation experiments, it is shown here that DUSP18 interacts with SAPK/JNK and dephosphorylates it both in vitro and in vivo. DUSP18 does not dephosphorylate p38 or p44ERK1. Furthermore, DUSP18 inhibits SAPK/JNK pathway in vivo. Based on these findings, DUSP18 appears to serve an important role by regulation of SAPK/JNK pathway.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, People's Republic of China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Wu
authors.forename: Shengdong
authors.initials: S
authors.lastname: Huang
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Sun
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gu
authors.forename: Fanglin
authors.initials: F
authors.lastname: Lu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Dai
authors.forename: Gang
authors.initials: G
authors.lastname: Yin
authors.forename: Liyun
authors.initials: L
authors.lastname: Sun
authors.forename: Dan
authors.initials: D
authors.lastname: Zheng
authors.forename: Chao
authors.initials: C
authors.lastname: Dou
authors.forename: Congjing
authors.initials: C
authors.lastname: Feng
authors.forename: Chaoneng
authors.initials: C
authors.lastname: Ji
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Yumin
authors.initials: Y
authors.lastname: Mao
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D054637:Dual-Specificity Phosphatases; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D012313:RNA; D048031:JNK Mitogen-Activated Protein Kinases; C473895:DUSP18 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases