The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways
Abstract
Functional discrimination between structurally similar self and foreign antigens is a main attribute of adaptive immunity. Here we describe two feedback mechanisms in T lymphocytes that together sharpen and amplify initial signaling differences related to the quality of T cell receptor (TCR) engagement. Weakly binding ligands predominantly trigger a negative feedback loop leading to rapid recruitment of the tyrosine phosphatase SHP-1, followed by receptor desensitization through inactivation of Lck kinase. In contrast, strongly binding ligands efficiently activate a positive feedback circuit involving Lck modification by ERK, preventing SHP-1 recruitment and allowing the long-lasting signaling necessary for gene activation. The characteristics of these pathways suggest that they constitute an important part of the mechanism allowing T cells to discriminate between self and foreign ligands.
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“DUSP6 dephosphorylates ERK, not only attenuating ERK signaling after TCR activation but also interfering with a forward feedback loop in TCR signaling”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Stefanová et al., 2003
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Cites
1 retracted
Parijs, L. V., Refaeli, Y., Lord, J. D., Nelson, B. H., Abbas, A. K., & Baltimore, D. (1999) · Immunity · doi:10.1016/s1074-7613(00)80103-x · Cited by 420
RetractedRAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement
Shinkai, Y. (1992) · Cell · doi:10.1016/0092-8674(92)90029-c · Cited by 2,651
SH2 domains recognize specific phosphopeptide sequences
Songyang, Z. (1993) · Cell · doi:10.1016/0092-8674(93)90404-e · Cited by 2,620
The Biochemical Basis of an All-or-None Cell Fate Switch in Xenopus Oocytes
Ferrell, J. E., & Machleder, E. M. (1998) · Science · doi:10.1126/science.280.5365.895 · Cited by 1,052
The Biochemistry and Cell Biology of Antigen Processing and Presentation
Germain, R. N., & Margulies, D. H. (1993) · Annual Review of Immunology · doi:10.1146/annurev.iy.11.040193.002155 · Cited by 1,003
Self-citationSeder, R. A., Paul, W. E., Davis, M. M., & Groth, B. F. D. S. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.4.1091 · Cited by 994
Kinetic proofreading in T-cell receptor signal transduction.
McKeithan, T. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.5042 · Cited by 964
Ding, L., Linsley, P. S., Huang, L. Y., Germain, R. N., & Shevach, E. M. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.3.1224 · Cited by 829
Self-citationDefective Thymocyte Maturation in p44 MAP Kinase (Erk 1) Knockout Mice
Pagès, G., Guérin, S., Grall, D., Bonino, F., Smith, A., Anjuere, F., Auberger, P., & Pouysségur, J. (1999) · Science · doi:10.1126/science.286.5443.1374 · Cited by 654
Receptor clustering as a cellular mechanism to control sensitivity
Bray, D., Levin, M. D., & Morton-Firth, C. J. (1998) · Nature · doi:10.1038/30018 · Cited by 613
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Smith-Garvin, J. E., Koretzky, G. A., & Jordan, M. S. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132706 · Cited by 2,144
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Li, Q.-J., Chau, J., Ebert, P. J. R., Sylvester, G., Min, H., Liu, G., Braich, R. S., Manoharan, M., Soutschek, J., Skare, P., et al. (2007) · Cell · doi:10.1016/j.cell.2007.03.008 · Cited by 1,165
T cell receptor (TCR) signaling in health and disease
Shah, K., Al-Haidari, A. A., Sun, J., & Kazi, J. U. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00823-w · Cited by 687
RAF-MEK-ERK pathway in cancer evolution and treatment
Ullah, R., Yin, Q., Snell, A. H., & Wan, L. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.05.010 · Cited by 553
The Immunological Synapse Balances T Cell Receptor Signaling and Degradation
Lee, K., Dinner, A. R., Tu, C., Campi, G., Raychaudhuri, S., Varma, R., Sims, T. N., Burack, R., Wu, H., Wang, J., et al. (2003) · Science · doi:10.1126/science.1086507 · Cited by 541
Metadata
- Authors
- Štefanová, I., Hemmer, B., Vergelli, M., Martin, R., Biddison, W. E., & Germain, R. N.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Germain, Ronald N.
- Venue
- Nature Immunology
- Published
- 2003-02-10
- Volume
- 4
- Issue
- 3
- Pages
- 248-254
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W1971692004
- Cited by
- 465
- References
- 63
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 15 · 2023: 13 · 2022: 14 · 2021: 19 · 2020: 19 · 2019: 19 · 2018: 11 · 2017: 16 · 2016: 17 · 2015: 14 · 2014: 28 · 2013: 24 · 2012: 28
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- T cell receptor signaling, ligand discrimination, Lck kinase, receptor desensitization, T cell activation, protein tyrosine phosphatase, signal amplification
- MeSH terms
- Animals, Humans, Ligands, Mice, Transgenic, Receptors, Antigen, T-Cell, Signal Transduction, Protein Tyrosine Phosphatases, CD8-Positive T-Lymphocytes, Mitogen-Activated Protein Kinases, Feedback, Physiological, Intracellular Signaling Peptides and Proteins, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 6
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