Stress-Activated Protein Kinase-Dependent Induction of c-fos by Cd²⁺ Is Mediated by MKK7

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• 作者：Ding ; Wei ; Templeton ; Douglas M.
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2000
• 出版时间：July 5, 2000
• 年：2000
• 卷：273
• 期：2
• 页码：718-722
• 全文大小：127 K

文摘

Exposure of mesangial cells to ionic Cd²⁺ induces the proto-oncogene c-fos, while activating both Erk and stress-activated protein kinase (SAPK) MAP kinase pathways. While we have previously used a pharmacological inhibitor of Erk activation to implicate involvement of this pathway in the induction of c-fos by Cd²⁺, the consequences of SAPK activation remained unknown. Here we use dominant negative inhibitors of the SAPK kinases, SEK1 and MKK7, to show that Cd²⁺ activates SAPK through MKK7, but that partial inhibition of SAPK alone is insufficient to significantly affect the magnitude of the Cd²⁺-dependent increase in c-fos mRNA. However, inhibition of Erk and SAPK pathways together abrogates the increase, suggesting that these pathways act in concert in the induction of c-fos by this toxic metal.