MHC class I and integrin ligation induce ERK activation via an mTORC2-dependent pathway
- 作者：Peter T. Jindra ; Yi-Ping Jin ; Rodrigo Jacamo ; Enrique Rozengurt ; Elaine F. Reed
- 关键词：MHC ; HLA class I ; ERK ; mTORC2 ; siRNA ; Endothelial cells ; Signal transduction
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：2 May 2008
- 卷：369
- 期：2
- 页码：781-787
- 文件大小：582 K
摘要
The aim of this study was to characterize the interaction between mTOR and ERK in primary endothelial cells (EC) following MHC class I and integrin ligation. Ligation of MHC class I molecules or integrins on the surface of EC leads to phosphorylation of ERK at Thr202/Tyr204. We utilized small interfering RNA (siRNA) blockade of mTOR and proteins involved in mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) to define a relationship between mTOR and ERK following MHC class I signaling. We found mTORC2 was responsible for MHC class I and integrin induced phosphorylation of ERK at Thr202/Tyr204. We corroborated these results demonstrating that long-term exposure to rapamycin also inhibited ERK pathway activation in response to MHC class I signaling. Our results demonstrate, for the first time, that engagement of either MHC class I or integrin on the surface of EC leads to ERK activation through an mTORC2-dependent pathway.