ArticleThe Journal of experimental medicine1997
Impaired plasma membrane targeting of Grb2-murine son of sevenless (mSOS) complex and differential activation of the Fyn-T cell receptor (TCR)-zeta-Cbl pathway mediate T cell hyporesponsiveness in autoimmune nonobese diabetic mice.
Article in The Journal of experimental medicine, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 67 citations in OpenAlex.
- Trial
- Protein Tyrosine Phosphatase SHP-1 Modulates T Cell Responses by Controlling Cbl-b Degradation.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Single-cell mass cytometry of TCR signaling: amplification of small initial differences results in low ERK activation in NOD mice.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity.Cell reports · 2012Article
- Thymic negative selection is functional in NOD mice.The Journal of experimental medicine · 2012Article
- Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes.Autoimmune diseases · 2010Article
- Quantitative phosphoproteomic analysis of T cell receptor signaling in diabetes prone and resistant mice.Journal of proteome research · 2010Article
- Altered thymic selection by overexpressing cellular FLICE inhibitory protein in T cells causes lupus-like syndrome in a BALB/c but not C57BL/6 strain.Cell death and differentiation · 2010Article
- Evidence for aberrant regulation of MAP kinase signal transduction pathway in peripheral blood mononuclear cells in patients with active celiac disease.Digestive diseases and sciences · 2009Article
- Genetic and Molecular Basis of QTL of Diabetes in Mouse: Genes and Polymorphisms.Current genomics · 2008Article
- Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling.Genome biology · 2007Article
- DNA vaccination with an insulin construct and a chimeric protein binding to both CTLA4 and CD40 ameliorates type 1 diabetes in NOD mice.Gene therapy · 2005Article
- Failure to censor forbidden clones of CD4 T cells in autoimmune diabetes.The Journal of experimental medicine · 2002Article
- Effect of dietary ghee--the anhydrous milk fat on lymphocytes in rats.Molecular and cellular biochemistry · 2001Article
- Beyond the RING: CBL proteins as multivalent adapters.Oncogene · 2001Review
- An abnormal adherence of monocytes to fibronectin in thyroid autoimmunity has consequences for cell polarization and the development of veiled cells.Clinical and experimental immunology · 2001Article
- Self-tolerance and the composition of T cell repertoire.Immunologic research · 2000Review
- Altered expression of tyrosine kinases of the Src and Syk families in human T-cell leukemia virus type 1-infected T-cell lines.Journal of virology · 1999Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonobese diabetic (NOD) mouse thymocytes are hyporesponsive to T cell antigen receptor (TCR)-mediated stimulation of proliferation, and this T cell hyporesponsiveness may be causal to the onset of autoimmune diabetes in NOD mice. We previously showed that TCR-induced NOD T cell hyporesponsiveness is associated with a block in Ras activation and defective signaling along the PKC/Ras/MAPK pathway. Here, we report that several sequential changes in TCR-proximal signaling events may mediate this block in Ras activation. We demonstrate that NOD T cell hyporesponsiveness is associated with the (a) enhanced TCR-beta-associated Fyn kinase activity and the differential activation of the Fyn-TCR-zeta-Cbl pathway, which may account for the impaired recruitment of ZAP70 to membrane-bound TCR-zeta; (b) relative inability of the murine son of sevenless (mSOS) Ras GDP releasing factor activity to translocate from the cytoplasm to the plasma membrane; and (c) exclusion of mSOS and PLC-gamma1 from the TCR-zeta-associated Grb2/pp36-38/ZAP70 signaling complex. Our data suggest that altered tyrosine phosphorylation and targeting of the Grb2/pp36-38/ZAP70 complex to the plasma membrane and cytoskeleton and the deficient association of mSOS with this Grb2-containing complex may block the downstream activation of Ras and Ras-mediated amplification of TCR/CD3-mediated signals in hyporesponsive NOD T cells. These findings implicate mSOS as an important mediator of downregulation of Ras signaling in hyporesponsive NOD T cells.
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