ArticleProceedings of the National Academy of Sciences of the United States of America2009
Differential impact of the CD45 juxtamembrane wedge on central and peripheral T cell receptor responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity.Immunology · 2012Pooled it
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- Inhibition of B cell receptor signaling induced by the human adenovirus species D E3/49K protein.Frontiers in immunology · 2024Article
- Clustering of phosphatase RPTPα promotes Src signaling and the arthritogenic action of synovial fibroblasts.Science signaling · 2023Article
- Antigen discrimination by T cells relies on size-constrained microvillar contact.Nature communications · 2023Article
- Metabolic preconditioning in CD4+ T cells restores inducible immune tolerance in lupus-prone mice.JCI insight · 2021Article
- Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Unbiased modifier screen reveals that signal strength determines the regulatory role murine TLR9 plays in autoantibody production.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- The structural wedge domain of the receptor-like tyrosine phosphatase CD45 enforces B cell tolerance by regulating substrate specificity.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling.Nature immunology · 2012Article
- Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases.Seminars in immunopathology · 2010Review
- The receptor protein tyrosine phosphatase LAR promotes R7 photoreceptor axon targeting by a phosphatase-independent signaling mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The cooperative activity of protein tyrosine kinases and phosphatases plays a central role in regulation of T cell receptor (TCR) signal strength. Perturbing this balance, and thus the threshold for TCR signals, has profound impacts on T cell development and function. We previously generated mice containing a point mutation in the juxtamembrane wedge of the receptor-like protein tyrosine phosphatase CD45. Demonstrating the critical negative regulatory function of the wedge, the CD45 E613R (WEDGE) mutation led to a lymphoproliferative disorder (LPD) and a lupus-like autoimmune syndrome. Using genetic, cellular, and biochemical approaches, we now demonstrate that the CD45 wedge influences T cell development and function. Consistent with increased TCR signal strength, WEDGE mice have augmented positive selection and enhanced sensitivity to the CD4-mediated disease experimental autoimmune encephalitis (EAE). These correspond with hyperresponsive calcium and pERK responses to TCR stimulation in thymocytes, but surprisingly, not in peripheral T cells, where these responses are actually depressed. Together, the data support a role for the CD45 wedge in regulation of T cell responses in vivo and suggest that its effects depend on cellular context.
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