ArticleMolecular and cellular biology2003
Gads/Grb2-mediated association with LAT is critical for the inhibitory function of Gab2 in T cells.
Article in Molecular and cellular biology, 2003. 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, 59 citations in OpenAlex.
- The Functional Properties and Physiological Roles of Signal-Transducing Adaptor Protein-2 in the Pathogenesis of Inflammatory and Immune Disorders.Biomedicines · 2022Review
- The Clinical Aspect of Adaptor Molecules in T Cell Signaling: Lessons Learnt From Inborn Errors of Immunity.Frontiers in immunology · 2021Review
- Naturally Occurring Genetic Alterations in Proximal TCR Signaling and Implications for Cancer Immunotherapy.Frontiers in immunology · 2021Review
- PI3Kδ Forms Distinct Multiprotein Complexes at the TCR Signalosome in Naïve and Differentiated CD4Frontiers in immunology · 2021Article
- Gab2 and Gab3 Redundantly Suppress Colitis by Modulating Macrophage and CD8Frontiers in immunology · 2019Article
- TNFR-associated factor 6 regulates TCR signaling via interaction with and modification of LAT adapter.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Protein tyrosine phosphatase SHP2 regulates TGF-β1 production in airway epithelia and asthmatic airway remodeling in mice.Allergy · 2012Article
- C terminus of the P2X7 receptor: treasure hunting.Purinergic signalling · 2011Article
- The nonphagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T cell receptor signaling.Science signaling · 2010Article
- The LAT story: a tale of cooperativity, coordination, and choreography.Cold Spring Harbor perspectives in biology · 2010Review
- Lymphoproliferative disorders involving T helper effector cells with defective LAT signalosomes.Seminars in immunopathology · 2010Review
- ZAP70: a master regulator of adaptive immunity.Seminars in immunopathology · 2010Review
- Regulation of lymphocyte development and activation by the LAT family of adapter proteins.Immunological reviews · 2009Review
- Function, regulation and pathological roles of the Gab/DOS docking proteins.Cell communication and signaling : CCS · 2009Article
- T cell receptor for antigen induces linker for activation of T cell-dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2.The Journal of experimental medicine · 2006Article
- Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP.The EMBO journal · 2005Article
- The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors.Cancer science · 2003Review
- The adaptor protein LAT serves as an integration node for signaling pathways that drive T cell activation.Wiley interdisciplinary reviews. Systems biology and medicineReview
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A docking protein, Gab2, is recruited to the vicinity of the TCR complex and inhibits downstream signaling by interaction with negative regulators. However, the molecular mechanisms of this recruitment remain unclear. We have found that Gab2 associates with LAT upon TCR stimulation and that LAT is essential for Gab2 phosphorylation. By analysis of several Gab2 mutants, the c-Met binding domain (MBD) of Gab2 was found to be both necessary and sufficient for stimulation-induced LAT binding. Within the MBD domain, a novel Grb2 SH3 binding motif, PXXXR, is critical for constitutive association with Gads/Grb2. Through this association, Gab2 is recruited to the lipid raft after TCR ligation and exerts inhibitory function. The in vivo significance of this association is illustrated by the fact that T-cell responses are impaired in transgenic mice expressing wild-type Gab2 but not in mice expressing mutant Gab2 lacking the motif. Furthermore, T cells from Gab2-deficient mice showed enhanced proliferative responses upon TCR stimulation. These results indicate that Gads/Grb2-mediated LAT association is critical for the inhibitory function of Gab2, implying that Gab2 induced in stimulated T cells may exert an efficient negative feedback loop by recruiting inhibitory molecules to the lipid raft and competing with SLP-76 through Gads binding.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.