ArticleThe EMBO journal2007
Efficient T-cell receptor signaling requires a high-affinity interaction between the Gads C-SH3 domain and the SLP-76 RxxK motif.
Article in The EMBO journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- SH3 domains selectively activate the PI3 kinase through non-conventional tertiary contacts.Communications biology · 2026Article
- Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T-Cell Adaptor Gads.European journal of immunology · 2025Article
- Functional selection in SH3-mediated activation of the PI3 kinase.bioRxiv : the preprint server for biology · 2024Article
- GRB2 dimerization mediated by SH2 domain-swapping is critical for T cell signaling and cytokine production.Scientific reports · 2023Article
- Facile Display of Homomultivalent Proteins forACS synthetic biology · 2023Article
- Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway.Frontiers in immunology · 2023Article
- Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics.Nature immunology · 2019Article
- Bridging the Gap: Modulatory Roles of the Grb2-Family Adaptor, Gads, in Cellular and Allergic Immune Responses.Frontiers in immunology · 2019Review
- Mathematical modeling identifies Lck as a potential mediator for PD-1 induced inhibition of early TCR signaling.PloS one · 2018Article
- Molecular mechanisms underlying the evolution of the slp76 signalosome.Scientific reports · 2017Article
- Exhaustive search of linear information encoding protein-peptide recognition.PLoS computational biology · 2017Article
- Multiplex matrix network analysis of protein complexes in the human TCR signalosome.Science signaling · 2016Article
- Evolution of domain-peptide interactions to coadapt specificity and affinity to functional diversity.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- An Interaction Library for the FcεRI Signaling Network.Frontiers in immunology · 2014Review
- Differential dynamic engagement within 24 SH3 domain: peptide complexes revealed by co-linear chemical shift perturbation analysis.PloS one · 2012Article
- A Conserved residue in the yeast Bem1p SH3 domain maintains the high level of binding specificity required for function.The Journal of biological chemistry · 2011Article
- A robust protocol to map binding sites of the 14-3-3 interactome: Cdc25C requires phosphorylation of both S216 and S263 to bind 14-3-3.Molecular & cellular proteomics : MCP · 2011Article
- The Role of SH2 Domain-containing Leukocyte Phosphoprotein of 76 kDa in the Regulation of Immune Cell Development and Function.Immune network · 2009Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The relationship between the binding affinity and specificity of modular interaction domains is potentially important in determining biological signaling responses. In signaling from the T-cell receptor (TCR), the Gads C-terminal SH3 domain binds a core RxxK sequence motif in the SLP-76 scaffold. We show that residues surrounding this motif are largely optimized for binding the Gads C-SH3 domain resulting in a high-affinity interaction (K(D)=8-20 nM) that is essential for efficient TCR signaling in Jurkat T cells, since Gads-mediated signaling declines with decreasing affinity. Furthermore, the SLP-76 RxxK motif has evolved a very high specificity for the Gads C-SH3 domain. However, TCR signaling in Jurkat cells is tolerant of potential SLP-76 crossreactivity, provided that very high-affinity binding to the Gads C-SH3 domain is maintained. These data provide a quantitative argument that the affinity of the Gads C-SH3 domain for SLP-76 is physiologically important and suggest that the integrity of TCR signaling in vivo is sustained both by strong selection of SLP-76 for the Gads C-SH3 domain and by a capacity to buffer intrinsic crossreactivity.
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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.