دورية أكاديمية
Nck recruitment to the TCR required for ZAP70 activation during thymic development.
| العنوان: | Nck recruitment to the TCR required for ZAP70 activation during thymic development. |
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| المؤلفون: | Borroto A; Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain., Arellano I, Dopfer EP, Prouza M, Suchànek M, Fuentes M, Orfao A, Schamel WW, Alarcón B |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2013 Feb 01; Vol. 190 (3), pp. 1103-12. Date of Electronic Publication: 2012 Dec 24. |
| 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 , CD3 Complex/*genetics , Lymphopoiesis/*physiology , Oncogene Proteins/*metabolism , Receptors, Antigen, T-Cell, alpha-beta/*metabolism , T-Lymphocyte Subsets/*metabolism , Thymocytes/*metabolism , Thymus Gland/*metabolism , ZAP-70 Protein-Tyrosine Kinase/*metabolism, Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Antigen Presentation ; CD3 Complex/immunology ; CD4 Antigens/analysis ; CD8 Antigens/analysis ; COS Cells ; Chlorocebus aethiops ; Enzyme Activation ; Female ; Gene Knock-In Techniques ; Hydrophobic and Hydrophilic Interactions ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Molecular Sequence Data ; Proline-Rich Protein Domains/genetics ; Protein Transport ; Recombinant Fusion Proteins/metabolism ; Thymocytes/cytology ; Thymus Gland/growth & development ; src Homology Domains |
| مستخلص: | The adaptor protein Nck is inducibly recruited through its SH3.1 domain to a proline-rich sequence (PRS) in CD3ε after TCR engagement. However, experiments with a knockin mutant bearing an 8-aa replacement of the PRS have indicated that Nck binding to the TCR is constitutive, and that it promotes the degradation of the TCR in preselection double-positive (DP) CD4(+)CD8(+) thymocytes. To clarify these discrepancies, we have generated a new knockin mouse line (KI-PRS) bearing a conservative mutation in the PRS resulting from the replacement of the two central prolines. Thymocytes of KI-PRS mice are partly arrested at each step at which pre-TCR or TCR signaling is required. The mutation prevents the trigger-dependent inducible recruitment of endogenous Nck to the TCR but does not impair TCR degradation. However, KI-PRS preselection DP thymocytes show impaired tyrosine phosphorylation of CD3ζ, as well as impaired recruitment of ZAP70 to the TCR and impaired ZAP70 activation. Our results indicate that Nck is recruited to the TCR in an inducible manner in DP thymocytes, and that this recruitment is required for the activation of early TCR-dependent events. Differences in the extent of PRS mutation could explain the phenotypic differences in both knockin mice. |
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| المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) 0 (CD3 Complex) 0 (CD4 Antigens) 0 (CD8 Antigens) 0 (Cd3e protein, mouse) 0 (Nck protein) 0 (Oncogene Proteins) 0 (Receptors, Antigen, T-Cell, alpha-beta) 0 (Recombinant Fusion Proteins) EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase) EC 2.7.10.2 (Zap70 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20121226 Date Completed: 20130326 Latest Revision: 20211021 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3549223 |
| DOI: | 10.4049/jimmunol.1202055 |
| PMID: | 23267019 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
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| DOI: | 10.4049/jimmunol.1202055 |