SHP-2-Erk signaling regulates Concanavalin A-dependent production of TIMP-2
- 作者：Md. Helal Uddin Biswas ; Hitoki Hitoki Hasegawa ; M. Aminur Rahman ; Pengyu Huang ; Naing Naing Mon ; A.R.M. Ruhul Amin ; Takeshi Senga ; Reiji Kannagi and Michinari Hamaguchi
- 关键词：SHP-2 ; TIMP-2 ; MAPK pathway ; Concanavalin A ; MMP-2 ; Signaling
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2006
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：29 September 2006
- 卷：348
- 期：3
- 页码：1145-1149
- 文件大小：148 K
摘要
To search for the signaling critical for the production of tissue inhibitor of metalloproteinase-2 (TIMP-2), we investigated the role of SHP-2 in TIMP-2 production with Concanavalin A (Con A)-treated cells. In wild-type fibroblasts, Con A-treatment dramatically activated TIMP-2 production. In contrast, production of TIMP-2 in response to Con A-treatment was severely impaired in cells expressing mutant SHP-2 whose 65 amino acids in the SH2-N domain were deleted. Con A-treatment activated dual signaling pathways, Erk and p38, in a SHP-2-dependent manner. Pretreatment of wild-type cells with U0126, a potent inhibitor of MEK1, significantly inhibited the production of TIMP-2, whereas SB203580, a specific inhibitor for p38, could not. Finally, expression of exogenous wild-type SHP-2 in SHP-2 mutant cells clearly rescued Erk activation and TIMP-2 production in response to Con A-treatment. Taken together, our results strongly suggest that SHP-2 plays a critical role as a positive modulator for the production of TIMP-2 via MEK1-Erk signaling in fibroblasts.