ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Disrupting the intermolecular self-association of Itk enhances T cell signaling.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Purification and characterization of full-length monomeric TEC family kinase, ITK.Protein expression and purification · 2025Article
- Regulation of Hematopoietic Cell Development and Function Through Phosphoinositides.Frontiers in immunology · 2018Review
- Article
- Rescue of the aggregation prone Itk Pleckstrin Homology domain by two mutations derived from the related kinases, Btk and Tec.Protein science : a publication of the Protein Society · 2012Article
- Structure of the interleukin-2 tyrosine kinase Src homology 2 domain; comparison between X-ray and NMR-derived structures.Acta crystallographica. Section F, Structural biology and crystallization communications · 2012Article
- Article
- In Vivo Consequences of Disrupting SH3-Mediated Interactions of the Inducible T-Cell Kinase.Journal of signal transduction · 2012Article
- Itk: the rheostat of the T cell response.Journal of signal transduction · 2011Article
- T-cell signaling regulated by the Tec family kinase, Itk.Cold Spring Harbor perspectives in biology · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The Tec family tyrosine kinase (Itk), is a key component of the TCR signaling pathway. Biochemical studies have shown that Itk activation requires recruitment of Itk 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. However, the regulation of Itk enzymatic activity by Itk domain interactions is not yet well understood. In this study, we show that full-length Itk self-associates in an intermolecular fashion. Using this information, we have designed an Itk variant that exhibits reduced self-association but maintains normal binding to exogenous ligands via each of its regulatory domains. When expressed in insect cells, the Itk substrate phospholipase Cgamma1 is phosphorylated more efficiently by the Itk variant than by wild-type Itk. Furthermore, expression of the Itk variant in primary murine T cells induced higher ERK activation and increased calcium flux following TCR stimulation compared with that of wild-type Itk. Our results indicate that the Tec kinase Itk is negatively regulated by intermolecular clustering and that disruption of this clustering leads to increased Itk kinase activity following TCR stimulation.
Indexed as
Identifiers
What OpenQuestion holds
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.