Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation

Nat Immunol. 2002 Aug;3(8):741-8. doi: 10.1038/ni817. Epub 2002 Jul 1.

Abstract

Fc epsilon RI activation of mast cells is thought to involve Lyn and Syk kinases proximal to the receptor and the signaling complex organized by the linker for activation of T cells (LAT). We report here that Fc epsilon RI also uses a Fyn kinase-dependent pathway that does not require Lyn kinase or the adapter LAT for its initiation, but is necessary for mast cell degranulation. Lyn-deficiency enhanced Fyn-dependent signals and degranulation, but inhibited the calcium response. Fyn-deficiency impaired degranulation, whereas Lyn-mediated signaling and calcium was normal. Thus, Fc epsilon RI-dependent mast cell degranulation involves cross-talk between Fyn and Lyn kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Cell Degranulation / immunology*
  • Crosses, Genetic
  • Enzyme Precursors / immunology
  • Female
  • Immunoblotting
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Mast Cells / immunology
  • Mast Cells / physiology*
  • Membrane Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphoproteins / immunology
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Precipitin Tests
  • Protein-Tyrosine Kinases / immunology
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / immunology*
  • Proto-Oncogene Proteins c-fyn
  • Receptors, IgE / immunology*
  • Signal Transduction / immunology*
  • Syk Kinase
  • src-Family Kinases / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Enzyme Precursors
  • Gab1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Lat protein, mouse
  • Membrane Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Receptors, IgE
  • Protein-Tyrosine Kinases
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn
  • Syk Kinase
  • Syk protein, mouse
  • lyn protein-tyrosine kinase
  • src-Family Kinases