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Dynamin 2 inhibits reactive oxygen species‐dependent EGF receptor transactivation by Angiotensin II in vascular smooth muscle cells
Author(s) -
Si Shuyi,
Xiao Chunling,
He Xiaobo,
Jiang Wei,
Su Lianfang,
Zuo Lian
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1006.7
Subject(s) - dynamin , microbiology and biotechnology , angiotensin ii , caveolae , transactivation , epidermal growth factor , caveolin , chemistry , signal transduction , vascular smooth muscle , receptor , caveolin 1 , biology , endocrinology , biochemistry , endocytosis , smooth muscle , gene , transcription factor
Angiotensin II (Ang II) induces transactivation of the epidermal growth factor (EGF) receptor (EGF‐R), which serves as a scaffold for various signaling molecules in vascular smooth muscle cells (VSMC). This response, which is critical for the full expression of the Ang II receptor signaling repertoire, is dependent on reactive oxygen species (ROS) derived from NAD(P)H oxidase and caveolin‐enriched membrane fractions. The dynamin family of large GTPases has been suggested in the formation of nascent vesicles in endocytic pathways. However, the specific effects of Dynamin 2 in ROS‐dependent AT 1 receptor (AT 1 R)‐mediated signaling remain unknown. Here we show that DN‐dynamin 2 and Dynamin 2 siRNA significantly inhibited Ang II‐induced EGF‐R transactivation. Detergent‐free cell fractionation demonstrates that EGF receptor (EGF‐R) is found basally in Caveolin‐enriched fractions (CF). Ang II stimulates AT 1 R movement into CF and egress of EGF‐R out of these microdomains. DN‐dynamin 2 dramatically blocks Ang II‐stimulated AT 1 R moving into and EGF‐R moving out of CF. These data suggest that Dynamin 2 specifically interferes with the ROS‐dependent signaling pathways which couple AT 1 R to the EGF‐R., thereby regulating the spatially‐ and temporally‐organized ROS‐dependent Ang II signaling in VSMCs.