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Published on: May 19, 2016
PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration
Yun-Ju Lai1, Weei-Chin Lin, Fang-Tsyr Lin
1Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
The Journal of Biological Chemistry
|June 27, 2007
Summary
Thyroid Hormone Receptor-interacting Protein 6 (TRIP6) controls cell migration. Fas-associated phosphatase-1 (PTPL1) dephosphorylates TRIP6, inhibiting its function and cell migration, revealing a feedback mechanism.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Thyroid Hormone Receptor-interacting Protein 6 (TRIP6) is a focal adhesion molecule.
- TRIP6 regulates lysophosphatidic acid (LPA)-induced cell migration via LPA2 receptor interaction.
- c-Src kinase phosphorylates TRIP6 at Tyr-55, promoting Crk binding and cell migration.
Purpose of the Study:
- Investigate the role of dephosphorylation in regulating TRIP6 function.
- Identify the phosphatase responsible for TRIP6 dephosphorylation.
- Elucidate the mechanism of PTPL1-mediated inhibition of TRIP6 in cell migration.
Main Methods:
- In vitro phosphatase assays using purified PTPL1 and TRIP6.
- Cellular studies to assess TRIP6 phosphorylation and localization.
- Analysis of protein-protein interactions between TRIP6 and PTPL1.
- Assessment of cell migration and morphological changes.
Main Results:
- PTPL1 dephosphorylates TRIP6 at phosphotyrosine 55.
- PTPL1 directly interacts with TRIP6 and requires its phosphatase activity.
- PTPL1 inhibits LPA-induced TRIP6 phosphorylation and Crk association.
- PTPL1 prevents TRIP6 turnover at focal adhesions, inhibiting cell migration.
Conclusions:
- PTPL1 acts as an inhibitory feedback regulator of TRIP6.
- PTPL1 dephosphorylation counteracts c-Src-mediated TRIP6 activation.
- This mechanism controls TRIP6 function in LPA-induced cell migration.
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