Negative regulation of Fc epsilonRI-mediated signaling and mast cell function by the adaptor protein LAX.
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.
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Related Subject Headings
- Signal Transduction
- Receptors, IgE
- Protein Subunits
- Protein Binding
- Phosphorylation
- Phosphatidylinositol 3-Kinases
- Mice
- Membrane Proteins
- Mast Cells
- MAP Kinase Signaling System
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Signal Transduction
- Receptors, IgE
- Protein Subunits
- Protein Binding
- Phosphorylation
- Phosphatidylinositol 3-Kinases
- Mice
- Membrane Proteins
- Mast Cells
- MAP Kinase Signaling System