title: LAT is essential for Fc(epsilon)RI-mediated mast cell activation.
abstract: The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement of T cells. LAT is also expressed in platelets, NK, and mast cells. Although LAT-deficient mice contain normal numbers of mast cells, we found that LAT-deficient mice were resistant to IgE-mediated passive systemic anaphylaxis. LAT-deficient bone marrow-derived mast cells (BMMC) showed normal growth and development. Whereas tyrosine phosphorylation of Fc(epsilon)RI, Syk, and Vav was intact in LAT-deficient BMMCs following Fc(epsilon)RI engagement, tyrosine phosphorylation of SLP-76, PLC-gamma1, and PLC-gamma2 and calcium mobilization were dramatically reduced. LAT-deficient BMMCs also exhibited profound defects in activation of MAPK, degranulation, and cytokine production after Fc(epsilon)RI cross-linking. These results show that LAT plays a critical role in Fc(epsilon)RI-mediated signaling in mast cells.
authors.affiliation: Laboratory of Cellular and Molecular Biology, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: S
authors.initials: S
authors.lastname: Saitoh
authors.forename: R
authors.initials: R
authors.lastname: Arudchandran
authors.forename: T S
authors.initials: TS
authors.lastname: Manetz
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: C L
authors.initials: CL
authors.lastname: Sommers
authors.forename: P E
authors.initials: PE
authors.lastname: Love
authors.forename: J
authors.initials: J
authors.lastname: Rivera
authors.forename: L E
authors.initials: LE
authors.lastname: Samelson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D010750:Phosphoproteins / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D017455:Receptors, IgE