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PEST Domain-Enriched Tyrosine Phosphatase (PEP) Regulation of Effector/Memory T Cells
Abstract
Protein tyrosine kinases and phosphatases cooperate to regulate normal immune cell function. We examined the role of PEST domain–enriched tyrosine phosphatase (PEP) in regulating T cell antigen–receptor function during thymocyte development and peripheral T cell differentiation. Although normal naïve T cell functions were retained in pep -deficient mice, effector/memory T cells demonstrated enhanced activation of Lck. In turn, this resulted in increased expansion and function of the effector/memory T cell pool, which was also associated with spontaneous development of germinal centers and elevated serum antibody levels. These results revealed a central role for PEP in negatively regulating specific aspects of T cell development and function.
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Cited by
Protein Tyrosine Phosphatases in the Human Genome
Alonso, A., Sasin, J., Bottini, N., Friedberg, I., Friedberg, I., Osterman, A., Godzik, A., Hunter, T., Dixon, J., & Mustelin, T. (2004) · Cell · doi:10.1016/j.cell.2004.05.018 · Cited by 1,886
Concannon, P., Rich, S. S., & Nepom, G. T. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0808284 · Cited by 510
T cell receptor signalling networks: branched, diversified and bounded
Brownlie, R. J., & Zamoyska, R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3403 · Cited by 453
PTPN22: the archetypal non-HLA autoimmunity gene
Stanford, S. M., & Bottini, N. (2014) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2014.109 · Cited by 227
Stanford, S. M., Krishnamurthy, D., Falk, M. D., Messina, R., Debnath, B., Li, S., Liu, T., Kazemi, R., Dahl, R., He, Y., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm101202j · Cited by 59
Self-citationLin, W. W., Yi, Z., Stunz, L. L., Maine, C. J., Sherman, L. A., & Bishop, G. A. (2015) · Science Signaling · doi:10.1126/scisignal.aaa5157 · Cited by 50
Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy
Castro-Sanchez, P., Teagle, A. R., Prade, S., & Zamoyska, R. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.608747 · Cited by 44
Metadata
- Authors
- Hasegawa, K., Martin, F., Huang, G., Tumas, D., Diehl, L., & Chan, A. C.
- Venue
- Science
- Published
- 2004-01-30
- Volume
- 303
- Issue
- 5658
- Pages
- 685-689
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2008649874
- Cited by
- 378
- References
- 0
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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