A peptide library approach identifies a specific inhibitor for the ZAP-70 protein tyrosine kinase.
Mol Cell
; 6(4): 969-74, 2000 Oct.
Article
em En
| MEDLINE
| ID: mdl-11090635
ABSTRACT
We utilized a novel peptide library approach to identify specific inhibitors of ZAP-70, a protein Tyr kinase involved in T cell activation. By screening more than 6 billion peptides oriented by a common Tyr residue for their ability to bind to ZAP-70, we determined a consensus optimal peptide. A Phe-for-Tyr substituted version of the peptide inhibited ZAP-70 protein Tyr kinase activity by competing with protein substrates (K(I) of 2 microM). The related protein Tyr kinases, Lck and Syk, were not significantly inhibited by the peptide. When introduced into intact T cells, the peptide blocked signaling downstream of ZAP-70, including ZAP-70-dependent gene induction, without affecting upstream Tyr phosphorylation. Thus, screening Tyr-oriented peptide libraries can identify selective peptide inhibitors of protein Tyr kinases.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Proteínas Tirosina Quinases
/
Biblioteca de Peptídeos
/
Inibidores Enzimáticos
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article