LAT is essential for Fc(epsilon)RI-mediated mast cell activation

Immunity. 2000 May;12(5):525-35. doi: 10.1016/s1074-7613(00)80204-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Carrier Proteins / immunology*
  • Mast Cells / immunology*
  • Membrane Proteins / immunology
  • Mice
  • Phosphoproteins / immunology*
  • Receptors, IgE / immunology*
  • Signal Transduction / immunology


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Lat protein, mouse
  • Membrane Proteins
  • Phosphoproteins
  • Receptors, IgE