ArticleJournal of molecular biology2007
Mechanism and functional significance of Itk autophosphorylation.
Article in Journal of molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Purification and characterization of full-length monomeric TEC family kinase, ITK.Protein expression and purification · 2025Article
- Regulation of the Tec family of non-receptor tyrosine kinases in cardiovascular disease.Cell death discovery · 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
- The SH3 domains of the protein kinases ITK and LCK compete for adjacent sites on T cell-specific adapter protein.The Journal of biological chemistry · 2019Article
- The Src module: an ancient scaffold in the evolution of cytoplasmic tyrosine kinases.Critical reviews in biochemistry and molecular biology · 2018Review
- Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation.Journal of molecular biology · 2015Article
- Targeting Interleukin-2-Inducible T-cell Kinase (ITK) in T-Cell Related Diseases.Postdoc journal : a journal of postdoctoral research and postdoctoral affairs · 2014Article
- Article
- Tyrosine phosphorylation within the SH3 domain regulates CAS subcellular localization, cell migration, and invasiveness.Molecular biology of the cell · 2011Article
- T-cell signaling regulated by the Tec family kinase, Itk.Cold Spring Harbor perspectives in biology · 2010Review
- Disrupting the intermolecular self-association of Itk enhances T cell signaling.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Itk tyrosine kinase substrate docking is mediated by a nonclassical SH2 domain surface of PLCgamma1.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- SH2-dependent autophosphorylation within the Tec family kinase Itk.Journal of molecular biology · 2009Article
- Proline isomerization preorganizes the Itk SH2 domain for binding to the Itk SH3 domain.Journal of molecular biology · 2009Article
- Conformational snapshots of Tec kinases during signaling.Immunological reviews · 2009Article
- ITK inhibitors in inflammation and immune-mediated disorders.Current topics in medicinal chemistry · 2009Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Tec family non-receptor tyrosine kinases (Itk, Btk, Tec, Rlk and Bmx) are characterized by the presence of an autophosphorylation site within the non-catalytic Src homology 3 (SH3) domain. The full-length Itk mutant containing phenylalanine in place of the autophosphorylated tyrosine has been studied in Itk-deficient primary T cells. These studies revealed that the non-phosphorylated enzyme restores Itk mediated signaling only partially. In spite of these insights, the precise role of the Tec kinase autophosphorylation site is unclear and the mechanism of the autophosphorylation reaction within the Tec kinases is not known. Here, we show both in vitro and in vivo that Itk autophosphorylation on Y180 within the SH3 domain occurs exclusively via an intramolecular, in cis mechanism. Using an in vitro kinase assay, we show that mutation of the Itk autophosphorylation site Y180 to Phe decreases kinase activity of the full-length enzyme by increasing Km for a peptide substrate. Moreover, mutation of Y180 to Glu, a residue chosen to mimic the phosphorylated tyrosine, alters the ligand-binding capability of the Itk SH3 domain in a ligand-dependent fashion. NMR chemical shift mapping gives residue-specific structural insight into the effect of the Y180E mutation on ligand binding. These data provide a molecular level context with which to interpret in vivo functional data and allow development of a structural model for Itk autophosphorylation.
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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.