title: Negative regulation of Fc epsilonRI-mediated signaling and mast cell function by the adaptor protein LAX.
abstract: 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.
authors: Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors: Minghua
authors: M
authors: Zhu
authors: Inmoo
authors: I
authors: Rhee
authors: Yan
authors: Y
authors: Liu
authors: Weiguo
authors: W
authors: Zhang