Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells.
Activation of the high affinity IgE receptor (Fc epsilon RI) of mast cells, a member of the antigen receptor family, leads to the release of allergic mediators, a critical event in the onset of immediate hypersensitivity. Stimulation of Fc epsilon RI results in the rapid association and activation of the Syk tyrosine kinase. Using Syk-deficient mast cells we show that they fail to degranulate, synthesize leukotrienes and secrete cytokines when stimulated through Fc epsilon RI, conclusively demonstrating an essential role for Syk in Fc epsilon RI signalling. Furthermore, our data strongly supports a model of Fc epsilon RI engagement leading to the sequential activation of the tyrosine kinases Lyn and then Syk. A similar mechanism is likely to apply to signal transduction through all members of the antigen receptor family.
Costello
P S
PS
National Institute for Medical Research, London, UK.
Turner
M
M
Walters
A E
AE
Cunningham
C N
CN
Bauer
P H
PH
Downward
J
J
Tybulewicz
V L
VL
D000818:Animals; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D015289:Leukotrienes / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D017455:Receptors, IgE / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D015289:Leukotrienes; D017455:Receptors, IgE; D012701:Serotonin; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D001619:beta-N-Acetylhexosaminidases