Inhibition of Lyn function in mast cell activation by SH3 domain binding peptides. Academic Article uri icon

Overview

abstract

  • While Lyn tyrosine kinase has been shown to be necessary for IgE-receptor (FcepsilonRI)-mediated mast cell activation, the mechanism of Lyn activation is not yet understood. Using a micro-electroporation technique to quantitatively introduce peptides into the cytosol of tumor mast cells, we show that proline-rich peptides that preferentially bind Src family SH3 domains block receptor-induced repetitive calcium spikes in a concentration dependent manner. The Src family member Lyn was the likely target, since a series of phage displaying derived peptides with increased Lyn SH3 domain binding specificity inhibited FcepsilonRI-mediated calcium signaling at concentrations consistent with binding to Lyn rather than other Src-type kinases. Furthermore, SH3 binding peptides prevented the plasma membrane translocation of a fluorescently labeled Syk tandem SH2 domain, which binds to phosphorylated FcepsilonRI, suggesting that the peptides specifically block the Lyn-mediated step by which FcepsilonRI cross-linking leads to receptor phosphorylation. Our study suggests that the binding of proline-rich peptides, or corresponding cellular interaction partners, to Lyn SH3 domain suppresses the Lyn-mediated phosphorylatation of FcepsilonRI and calcium signaling.

publication date

  • August 5, 1997

Research

keywords

  • Mast Cells
  • Peptides
  • src Homology Domains
  • src-Family Kinases

Identity

Scopus Document Identifier

  • 0030796010

Digital Object Identifier (DOI)

  • 10.1021/bi970781p

PubMed ID

  • 9235982

Additional Document Info

volume

  • 36

issue

  • 31