دورية أكاديمية
Nck Binds to the T Cell Antigen Receptor Using Its SH3.1 and SH2 Domains in a Cooperative Manner, Promoting TCR Functioning.
| العنوان: | Nck Binds to the T Cell Antigen Receptor Using Its SH3.1 and SH2 Domains in a Cooperative Manner, Promoting TCR Functioning. |
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| المؤلفون: | Paensuwan P; Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand;, Hartl FA; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency, University of Freiburg, Freiburg 79108, Germany;, Yousefi OS; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency, University of Freiburg, Freiburg 79108, Germany; Spemann Graduate School of Biology and Medicine, Albert Ludwigs University Freiburg, Freiburg 79104, Germany;, Ngoenkam J; Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand;, Wipa P; Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand;, Beck-Garcia E; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency, University of Freiburg, Freiburg 79108, Germany; International Max Planck Research School for Molecular and Cellular Biology, Freiburg 79108, Germany;, Dopfer EP; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency, University of Freiburg, Freiburg 79108, Germany;, Khamsri B; Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand;, Sanguansermsri D; Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand;, Minguet S; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency, University of Freiburg, Freiburg 79108, Germany;, Schamel WW; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency, University of Freiburg, Freiburg 79108, Germany; sutatipp@nu.ac.th wolfgang.schamel@biologie.uni-freiburg.de., Pongcharoen S; Centre of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand; Research Center for Academic Excellence in Petroleum, Petrochemical and Advanced Materials, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand; and Department of Medicine, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand sutatipp@nu.ac.th wolfgang.schamel@biologie.uni-freiburg.de. |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 Jan 01; Vol. 196 (1), pp. 448-58. Date of Electronic Publication: 2015 Nov 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Adaptor Proteins, Signal Transducing/*metabolism , Lymphocyte Activation/*immunology , Oncogene Proteins/*metabolism , Receptors, Antigen, T-Cell/*metabolism , T-Lymphocytes/*immunology, Adaptor Proteins, Signal Transducing/genetics ; Amino Acid Sequence ; Binding Sites ; CD3 Complex/metabolism ; Cell Line, Tumor ; Humans ; Jurkat Cells ; Oncogene Proteins/genetics ; Phosphorylation ; Proline-Rich Protein Domains ; Protein Binding ; Receptors, Antigen, T-Cell/immunology ; Signal Transduction/immunology ; src Homology Domains |
| مستخلص: | Ligand binding to the TCR causes a conformational change at the CD3 subunits to expose the CD3ε cytoplasmic proline-rich sequence (PRS). It was suggested that the PRS is important for TCR signaling and T cell activation. It has been shown that the purified, recombinant SH3.1 domain of the adaptor molecule noncatalytic region of tyrosine kinase (Nck) can bind to the exposed PRS of CD3ε, but the molecular mechanism of how full-length Nck binds to the TCR in cells has not been investigated so far. Using the in situ proximity ligation assay and copurifications, we show that the binding of Nck to the TCR requires partial phosphorylation of CD3ε, as it is based on two cooperating interactions. First, the SH3.1(Nck) domain has to bind to the nonphosphorylated and exposed PRS, that is, the first ITAM tyrosine has to be in the unphosphorylated state. Second, the SH2(Nck) domain has to bind to the second ITAM tyrosine in the phosphorylated state. Likewise, mutations of the SH3.1 and SH2 domains in Nck1 resulted in the loss of Nck1 binding to the TCR. Furthermore, expression of an SH3.1-mutated Nck impaired TCR signaling and T cell activation. Our data suggest that the exact pattern of CD3ε phosphorylation is critical for TCR functioning. (Copyright © 2015 by The American Association of Immunologists, Inc.) |
| التعليقات: | Erratum in: J Immunol. 2016 Jun 1;196(11):4833. (PMID: 27207808) |
| المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) 0 (CD3 Complex) 0 (CD3E protein, human) 0 (Nck protein) 0 (Oncogene Proteins) 0 (Receptors, Antigen, T-Cell) |
| تواريخ الأحداث: | Date Created: 20151122 Date Completed: 20160518 Latest Revision: 20171116 |
| رمز التحديث: | 20231215 |
| DOI: | 10.4049/jimmunol.1500958 |
| PMID: | 26590318 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
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| DOI: | 10.4049/jimmunol.1500958 |