ArticleBMC immunology2001
Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk.
Article in BMC immunology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 47 citations in OpenAlex.
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- Discovery of potent inhibitors for interleukin-2-inducible T-cell kinase: structure-based virtual screening and molecular dynamics simulation approaches.Journal of molecular modeling · 2013Article
- TEC and MAPK Kinase Signalling Pathways in T helper (TJournal of clinical & cellular immunology · 2012Article
- T-cell signaling regulated by the Tec family kinase, Itk.Cold Spring Harbor perspectives in biology · 2010Review
- Quantitative phosphoproteomic analysis of T cell receptor signaling in diabetes prone and resistant mice.Journal of proteome research · 2010Article
- ITK inhibitors in inflammation and immune-mediated disorders.Current topics in medicinal chemistry · 2009Review
- Quantitative time-resolved phosphoproteomic analysis of mast cell signaling.Journal of immunology (Baltimore, Md. : 1950) · 2007Article
- Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and regulates interferon-gamma gene transcription in Th1 cells.Clinical and experimental immunology · 2007Article
- Genome-scale identification of membrane-associated human mRNAs.PLoS genetics · 2006Article
- Genetic approaches to tyrosine kinase signaling pathways in the immune system.Immunologic research · 2003Review
- Vav1 transduces T cell receptor signals to the activation of phospholipase C-gamma1 via phosphoinositide 3-kinase-dependent and -independent pathways.The Journal of experimental medicine · 2002Article
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThe Tec family kinases are implicated in signaling from lymphocyte antigen receptors and are activated following phosphorylation by Src kinases. For most Tec kinases, this activation requires an interaction between their pleckstrin homology (PH) domains and the products of phosphoinositide 3-Kinase, which localizes Tec kinases to membrane RAFTs. Rlk/Txk is a Tec related kinase expressed in T cells that lacks a pleckstrin homology domain, having instead a palmitoylated cysteine-string motif. To evaluate Rlk's function in T cell receptor signaling cascades, we examined the requirements for Rlk localization and activation by Src family kinases.
resultsWe demonstrate that Rlk is also associated with RAFTs, despite its lack of a pleckstrin homology domain. Rlk RAFT association requires the cysteine-string motif and is independent of PI3 Kinase activity. We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association. Mutation of this tyrosine also prevents increased tyrosine phosphorylation of Rlk after stimulation of the T cell receptor, suggesting that Rlk is phosphorylated by Src family kinases in response to T cell receptor engagement.
conclusionsLike the other related Tec kinases, Rlk is associated with lipid RAFTs and can be phosphorylated and activated by Src family kinases, supporting a role for Rlk in signaling downstream of Src kinases in T cell activation.
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