ArticleProceedings of the National Academy of Sciences of the United States of America2009
Itk tyrosine kinase substrate docking is mediated by a nonclassical SH2 domain surface of PLCgamma1.
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 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- More than an attachment module: covalent inhibitor warheads influence BTK dynamics and function.bioRxiv : the preprint server for biology · 2026Article
- Purification and characterization of full-length monomeric TEC family kinase, ITK.Protein expression and purification · 2025Article
- Balancing activation and co-stimulation of CAR tunes signaling dynamics and enhances therapeutic potency.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The Conformational State of the BTK Substrate PLCγ Contributes to Ibrutinib Resistance.Journal of molecular biology · 2022Article
- Conformational switches that control the TEC kinase - PLCγ signaling axis.Journal of structural biology: X · 2022Review
- Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Lipid-targeting pleckstrin homology domain turns its autoinhibitory face toward the TEC kinases.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation.Journal of molecular biology · 2015Article
- Article
- Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells.Nature immunology · 2013Article
- Activation loop dynamics determine the different catalytic efficiencies of B cell- and T cell-specific tec kinases.Science signaling · 2013Article
- Substrate recognition of PLCγ1 via a specific docking surface on Itk.Journal of molecular biology · 2013Article
- A measured approach: determining the PLCγ1 docking site on Itk using a biochemical ruler.Journal of molecular biology · 2013Article
- Phosphotyrosine recognition domains: the typical, the atypical and the versatile.Cell communication and signaling : CCS · 2012Article
- LAT-independent Erk activation via Bam32-PLC-γ1-Pak1 complexes: GTPase-independent Pak1 activation.Molecular cell · 2012Article
- DEF6, a novel substrate for the Tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies.The Journal of biological chemistry · 2012Article
- Two closely spaced tyrosines regulate NFAT signaling in B cells via Syk association with Vav.Molecular and cellular biology · 2011Article
- Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells.The EMBO journal · 2011Article
- LKB1 regulates TCR-mediated PLCγ1 activation and thymocyte positive selection.The EMBO journal · 2011Article
- Structural basis for the interaction between the growth factor-binding protein GRB10 and the E3 ubiquitin ligase NEDD4.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Interleukin-2 tyrosine kinase (Itk) is a Tec family tyrosine kinase that mediates signaling processes after T cell receptor engagement. Activation of Itk requires recruitment to the membrane via its pleckstrin homology domain, phosphorylation of Itk by the Src kinase, Lck, and binding of Itk to the SLP-76/LAT adapter complex. After activation, Itk phosphorylates and activates phospholipase C-gamma1 (PLC-gamma1), leading to production of two second messengers, DAG and IP(3). We have previously shown that phosphorylation of PLC-gamma1 by Itk requires a direct, phosphotyrosine-independent interaction between the Src homology 2 (SH2) domain of PLC-gamma1 and the kinase domain of Itk. We now define this docking interface using a combination of mutagenesis and NMR spectroscopy and show that disruption of the Itk/PLCgamma1 docking interaction attenuates T cell signaling. The binding surface on PLCgamma1 that mediates recognition by Itk highlights a nonclassical binding activity of the well-studied SH2 domain providing further evidence that SH2 domains participate in important signaling interactions beyond recognition of phosphotyrosine.
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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.