Identification and Characterization of ERK MAP Kinase Phosphorylation Sites in Smad3

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• 作者：Isao Matsuura ; Guannan Wang ; Dongming He ; and Fang Liu
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：September 20, 2005
• 年：2005
• 卷：44
• 期：37
• 页码：12546 - 12553
• 全文大小：569K
• 年卷期：v.44,no.37(September 20, 2005)
• ISSN：1520-4995

文摘

Smad3 is phosphorylated by ERK MAP kinase upon EGF treatment. We have mapped theERK phosphorylation sites to Ser 207, Ser 203, and Thr 178 in Smad3. We show that, upon EGF treatment,Smad3 is rapidly phosphorylated in these sites, peaking at ~15-30 min and that MEK1 inhibitors PD98059and U0216 inhibit Smad3 phosphorylation induced by EGF. Ser 207 is the best ERK site in Smad3. Itsphosphorylation shows the highest EGF induction in Smad3. It is also a very sensitive site to EGF treatment,significantly responding to low concentrations of EGF. These three sites are also phosphorylated byrecombinant ERK2 in vitro. We have compared the kinetic parameters of Smad3 with those of ELK1 andMBP for ERK2. We further show that mutation of the ERK phosphorylation sites increases the ability ofSmad3 to stimulate a Smad target gene, suggesting that ERK phosphorylation inhibits Smad3 activity.