Journal article
Early Phosphorylation Kinetics of Proteins Involved in Proximal TCR-Mediated Signaling Pathways
The Journal of immunology (1950), Vol.175(4), pp.2449-2458
08/15/2005
DOI: 10.4049/jimmunol.175.4.2449
PMCID: PMC1414060
PMID: 16081816
Abstract
Activation of T cells via the stimulation of the TCR plays a central role in the adaptive immunological response. Although much is known about TCR-stimulated signaling pathways, there are still gaps in our knowledge about the kinetics and sequence of events during early activation and about the in vivo specificity of kinases involved in these proximal signaling pathways. This information is important not only for understanding the activation of signaling pathways important for T cell function but also for the development of drug targets and computer-based molecular models. In this study, phospho-specific Abs directed toward individual sites on signaling proteins were used to investigate the early phosphorylation kinetics of proteins involved in proximal TCR-induced pathways. These studies indicate that linker for activation of T cells' tyrosines have substantially different phosphorylation kinetics and that Src homology 2 domain-containing leukocyte protein of 76 kDa has rapid, transient phosphorylation kinetics compared to other proteins. In additions, we provide evidence that ZAP-70 is the primary in vivo kinase for LAT tyrosine 191 and that Itk plays a role in the phosphorylation of tyrosine 783 on phospholipase C-γ1. In total, these studies give new insight into the sequence, kinetics and specificity of early TCR-mediated signaling events that are vital for T cell activation.
Details
- Title: Subtitle
- Early Phosphorylation Kinetics of Proteins Involved in Proximal TCR-Mediated Signaling Pathways
- Creators
- Jon C. D Houtman - Laboratory of Cellular and Molecular Biology, National Cancer InstituteRichard A Houghtling - National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892Mira Barda-Saad - Laboratory of Cellular and Molecular Biology, National Cancer InstituteYoko Toda - Laboratory of Cellular and Molecular Biology, National Cancer InstituteLawrence E Samelson - Laboratory of Cellular and Molecular Biology, National Cancer Institute
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.175(4), pp.2449-2458
- DOI
- 10.4049/jimmunol.175.4.2449
- PMID
- 16081816
- PMCID
- PMC1414060
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 08/15/2005
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984094514602771
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