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Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites
Efrat Gottlieb-Abraham1, Dmitry E Shvartsman, John C Donaldson
1Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
Molecular Biology of the Cell
|October 18, 2013
Summary
Caveolin-1 stabilizes Src interactions with the plasma membrane. This involves Src phosphorylating Caveolin-1, enhancing Src activity and localization to focal adhesions, impacting cell dynamics.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Src kinase activity is regulated by plasma membrane interactions.
- Caveolin-1 (Cav-1) is a key component of caveolae and a target of Src phosphorylation.
- Both Src and Cav-1 are implicated in cell transformation, but their interaction mechanism is unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of Src and Cav-1 interaction.
- To investigate how Cav-1 modulates Src activity and membrane localization.
- To determine the role of Src-Cav-1 interaction in focal adhesion dynamics.
Main Methods:
- Utilized fluorescence recovery after photobleaching (FRAP) beam-size analysis.
- Performed co-immunoprecipitation, quantitative imaging, and far-Western studies.
- Employed cells expressing wild-type and mutant forms of Src-green fluorescent protein and Cav-1-monomeric red fluorescent protein.
Main Results:
- Demonstrated dynamic Src-plasma membrane interactions that are enhanced and stabilized by Cav-1.
- Revealed that Src phosphorylates Cav-1 at Tyr-14.
- Showed that the Src SH2 domain binds to phospho-Cav-1, leading to activated Src accumulation in focal adhesions.
Conclusions:
- Cav-1 enhances and stabilizes Src interactions with the plasma membrane.
- A novel mechanism of Src-Cav-1 coregulation involves Cav-1 phosphorylation by Src and subsequent SH2 domain binding.
- This interaction promotes activated Src accumulation in focal adhesions, potentially modulating focal adhesion dynamics.
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