Cargando…
The Vav Binding Site (Y315) in ZAP-70 Is Critical for Antigen Receptor–mediated Signal Transduction
Stimulation of antigen receptors in T and B cells leads to the activation of the Src and Syk families of protein tyrosine kinases (PTK). These PTKs subsequently phosphorylate numerous intracellular substrates, including the 95-kD protooncogene product Vav. Vav is essential for both T and B cell deve...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1997
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196311/ https://www.ncbi.nlm.nih.gov/pubmed/9151714 |
_version_ | 1782148037010784256 |
---|---|
author | Wu, Jun Zhao, Qihong Kurosaki, Tomohiro Weiss, Arthur |
author_facet | Wu, Jun Zhao, Qihong Kurosaki, Tomohiro Weiss, Arthur |
author_sort | Wu, Jun |
collection | PubMed |
description | Stimulation of antigen receptors in T and B cells leads to the activation of the Src and Syk families of protein tyrosine kinases (PTK). These PTKs subsequently phosphorylate numerous intracellular substrates, including the 95-kD protooncogene product Vav. Vav is essential for both T and B cell development and T and B cell antigen receptor–mediated signal transduction. After receptor ligation, Vav associates with phosphorylated Syk and ZAP-70 PTKs, an interaction that depends upon its SH2 domain. Here we demonstrate that a point mutation of tyrosine 315 (Y315F) in ZAP-70, a putative Vav SH2 domain binding site, eliminated the Vav– ZAP-70 interaction. Moreover, the Y315 mutation impaired the function of ZAP-70 in antigen receptor signaling. Surprisingly, this mutation also resulted in marked reduction in the tyrosine phosphorylation of ZAP-70, Vav, SLP-76, and Shc. These data demonstrate that the Vav binding site in ZAP-70 plays a critical role in antigen receptor–mediated signal transduction. |
format | Text |
id | pubmed-2196311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1997 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21963112008-04-16 The Vav Binding Site (Y315) in ZAP-70 Is Critical for Antigen Receptor–mediated Signal Transduction Wu, Jun Zhao, Qihong Kurosaki, Tomohiro Weiss, Arthur J Exp Med Brief Definitive Report Stimulation of antigen receptors in T and B cells leads to the activation of the Src and Syk families of protein tyrosine kinases (PTK). These PTKs subsequently phosphorylate numerous intracellular substrates, including the 95-kD protooncogene product Vav. Vav is essential for both T and B cell development and T and B cell antigen receptor–mediated signal transduction. After receptor ligation, Vav associates with phosphorylated Syk and ZAP-70 PTKs, an interaction that depends upon its SH2 domain. Here we demonstrate that a point mutation of tyrosine 315 (Y315F) in ZAP-70, a putative Vav SH2 domain binding site, eliminated the Vav– ZAP-70 interaction. Moreover, the Y315 mutation impaired the function of ZAP-70 in antigen receptor signaling. Surprisingly, this mutation also resulted in marked reduction in the tyrosine phosphorylation of ZAP-70, Vav, SLP-76, and Shc. These data demonstrate that the Vav binding site in ZAP-70 plays a critical role in antigen receptor–mediated signal transduction. The Rockefeller University Press 1997-05-19 /pmc/articles/PMC2196311/ /pubmed/9151714 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report Wu, Jun Zhao, Qihong Kurosaki, Tomohiro Weiss, Arthur The Vav Binding Site (Y315) in ZAP-70 Is Critical for Antigen Receptor–mediated Signal Transduction |
title | The Vav Binding Site (Y315) in ZAP-70 Is Critical for Antigen Receptor–mediated Signal Transduction |
title_full | The Vav Binding Site (Y315) in ZAP-70 Is Critical for Antigen Receptor–mediated Signal Transduction |
title_fullStr | The Vav Binding Site (Y315) in ZAP-70 Is Critical for Antigen Receptor–mediated Signal Transduction |
title_full_unstemmed | The Vav Binding Site (Y315) in ZAP-70 Is Critical for Antigen Receptor–mediated Signal Transduction |
title_short | The Vav Binding Site (Y315) in ZAP-70 Is Critical for Antigen Receptor–mediated Signal Transduction |
title_sort | vav binding site (y315) in zap-70 is critical for antigen receptor–mediated signal transduction |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196311/ https://www.ncbi.nlm.nih.gov/pubmed/9151714 |
work_keys_str_mv | AT wujun thevavbindingsitey315inzap70iscriticalforantigenreceptormediatedsignaltransduction AT zhaoqihong thevavbindingsitey315inzap70iscriticalforantigenreceptormediatedsignaltransduction AT kurosakitomohiro thevavbindingsitey315inzap70iscriticalforantigenreceptormediatedsignaltransduction AT weissarthur thevavbindingsitey315inzap70iscriticalforantigenreceptormediatedsignaltransduction AT wujun vavbindingsitey315inzap70iscriticalforantigenreceptormediatedsignaltransduction AT zhaoqihong vavbindingsitey315inzap70iscriticalforantigenreceptormediatedsignaltransduction AT kurosakitomohiro vavbindingsitey315inzap70iscriticalforantigenreceptormediatedsignaltransduction AT weissarthur vavbindingsitey315inzap70iscriticalforantigenreceptormediatedsignaltransduction |