ArticleProceedings of the National Academy of Sciences of the United States of America1997
Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the Pleckstrin homology domain of inducible T cell kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 178 citations in OpenAlex.
- Sequential Regulation of Neurovascular Bone Regeneration in Large Bone Defects Using Black Phosphorus-Europium Nanosheet Integrated TPMS Biomimetic Scaffold with Photo-Controlled Ion Release.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Differential regulatory effects of the N-terminal region in SYK-fusion kinases reveal unique activation-inducible nuclear translocation of ITK-SYK.Scientific reports · 2025Article
- IL2-inducible T-cell Kinase is Required for HBV-induced Type T Interferon Expression and Antiviral Response.Journal of clinical and translational hepatology · 2023Article
- TCR/ITK Signaling in Type 1 Regulatory T cells.Advances in experimental medicine and biology · 2021Article
- Role of the IL-2 inducible tyrosine kinase ITK and its inhibitors in disease pathogenesis.Journal of molecular medicine (Berlin, Germany) · 2020Review
- TCR Signal Strength and Antigen Affinity Regulate CD8Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Transforming growth factor β (TGF-β) receptor signaling regulates kinase networks and phosphatidylinositol metabolism during T-cell activation.The Journal of biological chemistry · 2020Article
- Tuning T helper cell differentiation by ITK.Biochemical Society transactions · 2020Review
- Targeting Interleukin-2-Inducible T-Cell Kinase (ITK) Differentiates GVL and GVHD in Allo-HSCT.Frontiers in immunology · 2020Article
- A switch in nucleotide affinity governs activation of the Src and Tec family kinases.Scientific reports · 2017Article
- Versican G1 domain enhances adenoviral-mediated transgene expression and can be modulated by inhibitors of the Janus kinase (JAK)/STAT and Src family kinase pathways.The Journal of biological chemistry · 2017Article
- An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2-Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid Recognition.Biochemistry · 2017Article
- The multifaceted role of PIP2 in leukocyte biology.Cellular and molecular life sciences : CMLS · 2015Review
- Allele-sensitive mutant, Itkas, reveals that Itk kinase activity is required for Th1, Th2, Th17, and iNKT-cell cytokine production.European journal of immunology · 2015Article
- The signaling symphony: T cell receptor tunes cytokine-mediated T cell differentiation.Journal of leukocyte biology · 2015Review
- SRC homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) N-terminal tyrosine residues regulate a dynamic signaling equilibrium involving feedback of proximal T-cell receptor (TCR) signaling.Molecular & cellular proteomics : MCP · 2015Article
- People's instinctive travels and the paths to science.Molecular biology of the cell · 2014Article
- Targeting Interleukin-2-Inducible T-cell Kinase (ITK) in T-Cell Related Diseases.Postdoc journal : a journal of postdoctoral research and postdoctoral affairs · 2014Article
- BMX acts downstream of PI3K to promote colorectal cancer cell survival and pathway inhibition sensitizes to the BH3 mimetic ABT-737.Neoplasia (New York, N.Y.) · 2014Article
- The zinc-binding region of IL-2 inducible T cell kinase (Itk) is required for interaction with Gα13 and activation of serum response factor.The international journal of biochemistry & cell biology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The Tec family of tyrosine kinases are involved in signals emanating from cytokine receptors, antigen receptors, and other lymphoid cell surface receptors. One family member, ITK (inducible T cell kinase), is involved in T cell activation and can be activated by the T cell receptor and the CD28 cell surface receptor. This stimulation of tyrosine phosphorylation and activation of ITK can be mimicked by the Src family kinase Lck. We have explored the mechanism of this requirement for Src family kinases in the activation of ITK. We found that coexpression of ITK and Src results in increased membrane association, tyrosine phosphorylation and activation of ITK, which could be blocked by inhibitors of the lipid kinase phosphatidylinositol 3-kinase (PI 3-kinase) as well as overexpression of the p85 subunit of PI 3-kinase. Removal of the Pleckstrin homology domain (PH) of ITK resulted in a kinase that could no longer be induced to localize to the membrane or be activated by Src. The PH of ITK was also able to bind inositol phosphates phosphorylated at the D3 position. Membrane targeting of ITK without the PH recovered its ability to be activated by Src. These results suggest that ITK can be activated by a combination of Src and PI 3-kinase.
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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 Socratic graph.