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Updated: Dec 20, 2025
09:40
Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
Published on: September 28, 2018
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PTPN22 interacts with EB1 to regulate T-cell receptor signaling
Xiaonan Zhang1, Yang Yu1, Bin Bai1
1Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang, P.R. China.
Summary
The PTPN22 gene regulates T-cell receptor (TCR) signaling by dephosphorylating end-binding protein 1 (EB1). This interaction impacts T-cell activation markers and cytokine production, offering insights into autoimmune diseases.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- PTPN22 (protein tyrosine phosphatase, non-receptor type 22) negatively regulates T-cell receptor (TCR) signaling.
- End-binding protein 1 (EB1) phosphorylation is linked to TCR activation.
Purpose of the Study:
- To investigate the interaction between PTPN22 and EB1.
- To elucidate the role of PTPN22 in regulating TCR signaling through EB1.
Main Methods:
- Yeast two-hybrid assays
- Mass spectrometry
- Protein binding assays
- Western blotting
Main Results:
- EB1 was identified as a protein associated with PTPN22.
- EB1 binds to the P1 domain of PTPN22, competing with CSK.
- PTPN22 dephosphorylates EB1 at Y247, reducing T-cell activation markers (CD25, CD69), TCR signaling molecule phosphorylation (ZAP-70, LAT, Erk), NFAT activity, and IL-2 secretion.
- The PTPN22-R620W variant does not affect EB1 association.
Conclusions:
- PTPN22 directly regulates TCR signaling by dephosphorylating EB1.
- This mechanism is crucial for controlling T-cell immune responses.
- Understanding this interaction provides insights into PTPN22-related autoimmune diseases.
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