Negative regulation of Fc epsilonRI-mediated signaling and mast cell function by the adaptor protein LAX.

Journal Article

LAX is a transmembrane adaptor protein that is expressed in both T and B cells. Upon stimulation via the antigen receptors, it is tyrosine-phosphorylated and binds Grb2 and the p85 subunit of phosphatidylinositol 3-kinase. Disruption of the Lax gene causes hyperresponsiveness in T and B lymphocytes. Here, we showed that LAX was also expressed in mast cells. Upon engagement of the Fc epsilonRI, LAX was also phosphorylated and interacted with Grb2 and p85. LAX-deficient mast cells were hyperresponsive to stimulation via the Fc epsilonRI, as evidenced by enhanced degranulation, p38 MAPK, Akt, and phosphatidylinositol 3-kinase activation. This hyperresponsiveness was likely a consequence of reduced LAB expression after sensitization of mast cells with anti-dinitrophenyl IgE. In addition, Fc epsilonRI-mediated cytokine production and cell survival were also enhanced. These data suggested that LAX negatively regulates mast cell function.

Full Text

Duke Authors

Cited Authors

  • Zhu, M; Rhee, I; Liu, Y; Zhang, W

Published Date

  • July 7, 2006

Published In

Volume / Issue

  • 281 / 27

Start / End Page

  • 18408 - 18413

PubMed ID

  • 16672218

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M601535200

Language

  • eng

Conference Location

  • United States