Dual specificity phosphotase 18, interacting with SAPK, dephosphorylates SAPK and inhibits SAPK/JNK signal pathway in vivo.
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.
Wu
Qihan
Q
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, People's Republic of China.
Huang
Shengdong
S
Sun
Yaqiong
Y
Gu
Shaohua
S
Lu
Fanglin
F
Dai
Jianfeng
J
Yin
Gang
G
Sun
Liyun
L
Zheng
Dan
D
Dou
Chao
C
Feng
Congjing
C
Ji
Chaoneng
C
Xie
Yi
Y
Mao
Yumin
Y
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
D012313:RNA; D048031:JNK Mitogen-Activated Protein Kinases; C473895:DUSP18 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases