ArticleProceedings of the National Academy of Sciences of the United States of America2008
Tyr130 phosphorylation triggers Syk release from antigen receptor by long-distance conformational uncoupling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- An electrostatic network with strong connectivity is a phospho-sensor for regulating affinity of Syk-receptor association.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The mechanism of allosteric activation of SYK kinase derived from multiple phospho-ITAM-bound structures.Structure (London, England : 1993) · 2024Article
- Protein-Sequence-Based Search of Nonreceptor ITAM-Like Regions to Identify Cytosolic Syk-Recruiting Proteins.The journal of physical chemistry. B · 2024Article
- New insights into SYK targeting in solid tumors.Trends in pharmacological sciences · 2024Review
- The spleen tyrosine kinase (SYK): A crucial therapeutic target for diverse liver diseases.Heliyon · 2022Review
- Dephosphorylation accelerates the dissociation of ZAP70 from the T cell receptor.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases.Protein science : a publication of the Protein Society · 2021Article
- Role of spleen tyrosine kinase in liver diseases.World journal of gastroenterology · 2020Review
- Combinatorial diversity of Syk recruitment driven by its multivalent engagement with FcεRIγ.Molecular biology of the cell · 2019Article
- A reevaluation of the spleen tyrosine kinase (SYK) activation mechanism.The Journal of biological chemistry · 2019Article
- Entropic allostery dominates the phosphorylation-dependent regulation of Syk tyrosine kinase release from immunoreceptor tyrosine-based activation motifs.Protein science : a publication of the Protein Society · 2018Article
- Modulation of BCR Signaling by the Induced Dimerization of Receptor-Associated SYK.Antibodies (Basel, Switzerland) · 2017Article
- Timescale Separation of Positive and Negative Signaling Creates History-Dependent Responses to IgE Receptor Stimulation.Scientific reports · 2017Article
- Differential mast cell outcomes are sensitive to FcεRI-Syk binding kinetics.Molecular biology of the cell · 2017Article
- A cycle of Zap70 kinase activation and release from the TCR amplifies and disperses antigenic stimuli.Nature immunology · 2017Article
- TULA-2 Protein Phosphatase Suppresses Activation of Syk through the GPVI Platelet Receptor for Collagen by Dephosphorylating Tyr(P)346, a Regulatory Site of Syk.The Journal of biological chemistry · 2016Article
- Insights into the allosteric regulation of Syk association with receptor ITAM, a multi-state equilibrium.Physical chemistry chemical physics : PCCP · 2016Article
- Analysis of Multidomain Protein Dynamics.Journal of chemical theory and computation · 2016Article
- Survey of phosphorylation near drug binding sites in the Protein Data Bank (PDB) and their effects.Proteins · 2015Article
- Activation pathway of Src kinase reveals intermediate states as targets for drug design.Nature communications · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The Syk protein-tyrosine kinase plays a major role in signaling through the B cell receptor for antigen (BCR). Syk binds the receptor via its tandem pair of SH2 domains interacting with a doubly phosphorylated immunoreceptor tyrosine-based activation motif (dp-ITAM) of the BCR complex. Upon phosphorylation of Tyr-130, which lies between the two SH2 domains distant to the phosphotyrosine binding sites, Syk dissociates from the receptor. To understand the structural basis for this dissociation, we investigated the structural and dynamic characteristics of the wild type tandem SH2 region (tSH2) and a variant tandem SH2 region (tSH2(pm)) with Tyr-130 substituted by Glu to permanently introduce a negative charge at this position. NMR heteronuclear relaxation experiments, residual dipolar coupling measurements and analytical ultracentrifugation revealed substantial differences in the hydrodynamic behavior of tSH2 and tSH2(pm). Although the two SH2 domains in tSH2 are tightly associated, the two domains in tSH2(pm) are partly uncoupled and tumble in solution with a faster correlation time. In addition, the equilibrium dissociation constant for the binding of tSH2(pm) to dp-ITAM (1.8 microM) is significantly higher than that for the interaction between dp-ITAM and tSH2 but is close to that for a singly tyrosine-phosphorylated peptide binding to a single SH2 domain. Experimental data and hydrodynamic calculations both suggest a loss of domain-domain contacts and change in relative orientation upon the introduction of a negative charge on residue 130. A long-distance structural mechanism by which the phosphorylation of Y130 negatively regulates the interaction of Syk with immune receptors is proposed.
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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.