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Trihydrophobin 1 phosphorylation by c-Src regulates MAPK/ERK signaling and cell migration
Weibin Wu1, Zhichao Sun, Jingwen Wu
1Gene Research Center, Shanghai Medical College, Fudan University, Shanghai, China.
Plos One
|January 13, 2012
Summary
c-Src phosphorylation of trihydrophobin 1 (TH1) disrupts its interaction with A-Raf and PAK1. This reduces TH1
Area of Science:
- Cell biology
- Molecular signaling
- Cancer research
Background:
- c-Src kinase activates the Ras-MAPK/ERK pathway, promoting cell migration.
- Trihydrophobin 1 (TH1) inhibits MAPK/ERK and cell migration by interacting with A-Raf and PAK1.
Purpose of the Study:
- To investigate the interaction between c-Src and TH1.
- To elucidate the role of TH1 phosphorylation in regulating MAPK/ERK signaling and cell migration.
Main Methods:
- GST-pull down assay
- Coimmunoprecipitation
- Confocal microscopy
- In vitro and in vivo phosphorylation assays
Main Results:
- c-Src directly interacts with TH1.
- c-Src phosphorylates TH1 at Tyr-6, reducing its binding to A-Raf and PAK1.
- TH1 phosphorylation diminishes its inhibitory effect on MAPK/ERK signaling, enhancing c-Src-mediated cell migration.
- EGF and estrogen treatments induce TH1 tyrosine phosphorylation.
Conclusions:
- Tyrosine phosphorylation of TH1 by c-Src is a novel regulatory mechanism for Ras/Raf/MEK/ERK signaling.
- This phosphorylation modulates TH1's interaction with A-Raf and PAK1, impacting cell migration.
- The findings reveal a new pathway for controlling cell signaling and migration.
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