Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex.
During antigen recognition by T cells, CD4 and the T-cell receptor (TCR)/CD3/zeta complex are thought to interact with the same major histocompatibility complex II molecule in a stable ternary complex. Evidence has suggested that the association of CD4 with TCR/CD3/zeta requires the interaction of t...
| Główni autorzy: | , , , |
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| Format: | Journal article |
| Język: | English |
| Wydane: |
1995
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| _version_ | 1826300019789004800 |
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| author | Thome, M Duplay, P Guttinger, M Acuto, O |
| author_facet | Thome, M Duplay, P Guttinger, M Acuto, O |
| author_sort | Thome, M |
| collection | OXFORD |
| description | During antigen recognition by T cells, CD4 and the T-cell receptor (TCR)/CD3/zeta complex are thought to interact with the same major histocompatibility complex II molecule in a stable ternary complex. Evidence has suggested that the association of CD4 with TCR/CD3/zeta requires the interaction of the protein tyrosine kinase p56lck with CD4. We have taken a biochemical approach to understand the mechanism by which p56lck and, in particular, its src homology (SH) 2 domain contributes to the association of CD4 with TCR/CD3/zeta during activation. We have previously shown that the p56lck SH2 domain binds directly to tyrosine-phosphorylated ZAP-70. Here we formally demonstrate the in vivo association of p56lck with the homologous protein tyrosine kinases Syk and ZAP-70 after CD3 stimulation of Jurkat cells. A tyrosine-phosphorylated peptide containing the sequence predicted to be optimal for binding to the SH2 domain of src family kinases specifically competes for this association, indicating that tyrosine-phosphorylated ZAP-70 and Syk bind to p56lck by an SH2-mediated interaction. We also show that the same peptide is able to compete for the activation-dependent TCR/CD4 association in Jurkat cells. Moreover, ZAP-70 and CD4 cocap only after CD3 stimulation in human T lymphoblasts. We propose that the interaction of the p56lck SH2 domain with zeta-associated tyrosine-phosphorylated ZAP-70 and/or Syk enables CD4 to associate with antigen-stimulated TCR/CD3/zeta complexes. |
| first_indexed | 2024-03-07T05:10:46Z |
| format | Journal article |
| id | oxford-uuid:db76a84d-970b-4393-a075-7ca7915eefef |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:10:46Z |
| publishDate | 1995 |
| record_format | dspace |
| spelling | oxford-uuid:db76a84d-970b-4393-a075-7ca7915eefef2022-03-27T09:10:49ZSyk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:db76a84d-970b-4393-a075-7ca7915eefefEnglishSymplectic Elements at Oxford1995Thome, MDuplay, PGuttinger, MAcuto, ODuring antigen recognition by T cells, CD4 and the T-cell receptor (TCR)/CD3/zeta complex are thought to interact with the same major histocompatibility complex II molecule in a stable ternary complex. Evidence has suggested that the association of CD4 with TCR/CD3/zeta requires the interaction of the protein tyrosine kinase p56lck with CD4. We have taken a biochemical approach to understand the mechanism by which p56lck and, in particular, its src homology (SH) 2 domain contributes to the association of CD4 with TCR/CD3/zeta during activation. We have previously shown that the p56lck SH2 domain binds directly to tyrosine-phosphorylated ZAP-70. Here we formally demonstrate the in vivo association of p56lck with the homologous protein tyrosine kinases Syk and ZAP-70 after CD3 stimulation of Jurkat cells. A tyrosine-phosphorylated peptide containing the sequence predicted to be optimal for binding to the SH2 domain of src family kinases specifically competes for this association, indicating that tyrosine-phosphorylated ZAP-70 and Syk bind to p56lck by an SH2-mediated interaction. We also show that the same peptide is able to compete for the activation-dependent TCR/CD4 association in Jurkat cells. Moreover, ZAP-70 and CD4 cocap only after CD3 stimulation in human T lymphoblasts. We propose that the interaction of the p56lck SH2 domain with zeta-associated tyrosine-phosphorylated ZAP-70 and/or Syk enables CD4 to associate with antigen-stimulated TCR/CD3/zeta complexes. |
| spellingShingle | Thome, M Duplay, P Guttinger, M Acuto, O Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex. |
| title | Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex. |
| title_full | Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex. |
| title_fullStr | Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex. |
| title_full_unstemmed | Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex. |
| title_short | Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex. |
| title_sort | syk and zap 70 mediate recruitment of p56lck cd4 to the activated t cell receptor cd3 zeta complex |
| work_keys_str_mv | AT thomem sykandzap70mediaterecruitmentofp56lckcd4totheactivatedtcellreceptorcd3zetacomplex AT duplayp sykandzap70mediaterecruitmentofp56lckcd4totheactivatedtcellreceptorcd3zetacomplex AT guttingerm sykandzap70mediaterecruitmentofp56lckcd4totheactivatedtcellreceptorcd3zetacomplex AT acutoo sykandzap70mediaterecruitmentofp56lckcd4totheactivatedtcellreceptorcd3zetacomplex |