A peptide library approach identifies a specific inhibitor for the ZAP-70 protein tyrosine kinase Academic Article uri icon

Overview

MeSH Major

  • Enzyme Inhibitors
  • Peptide Library
  • Peptides
  • Protein-Tyrosine Kinases

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.

publication date

  • December 28, 2000

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 11090635

Additional Document Info

start page

  • 969

end page

  • 74

volume

  • 6

number

  • 4