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PTPN4 negatively regulates CrkI in human cell lines
Juan Zhou1, Bingbing Wan, Jingxuan Shan
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
Cellular & Molecular Biology Letters
|May 14, 2013
Summary
Protein tyrosine phosphatase non-receptor type 4 (PTPN4) inhibits cell growth by interacting with CrkI. PTPN4 dephosphorylates CrkI, negatively regulating cell proliferation and motility.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Protein tyrosine phosphatase non-receptor type 4 (PTPN4) is widely expressed.
- PTPN4 overexpression inhibits cell growth, but its interacting partners are unknown.
Purpose of the Study:
- To identify proteins interacting with PTPN4.
- To elucidate the role of PTPN4-CrkI interaction in cell growth regulation.
Main Methods:
- Yeast two-hybrid screening to identify interacting proteins.
- GST pull-down, co-immunoprecipitation, and co-localization assays to confirm interactions.
- siRNA-mediated knockdown and ectopic expression studies in HEK293T and Hep3B cells.
Main Results:
- CrkI was identified as a PTPN4-interacting protein.
- The SH3 domain of CrkI and a proline-rich region of PTPN4 mediate the interaction.
- PTPN4 inhibits CrkI-mediated proliferation and wound healing, while PTPN4 knockdown enhances CrkI-mediated cell growth and motility.
- PTPN4 reduces CrkI phosphorylation levels.
Conclusions:
- PTPN4 negatively regulates cell proliferation and motility.
- PTPN4 exerts its function through the dephosphorylation of CrkI.
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