Integrated signalling pathways for mast-cell activation.
Mast-cell activation mediated by the high-affinity receptor for IgE (FcepsilonRI) is considered to be a key event in the allergic inflammatory response. However, in a physiological setting, other receptors, such as KIT, might also markedly influence the release of mediators by mast cells. Recent studies have provided evidence that FcepsilonRI-dependent degranulation is regulated by two complementary signalling pathways, one of which activates phospholipase Cgamma and the other of which activates phosphatidylinositol 3-kinase, using specific transmembrane and cytosolic adaptor molecules. In this Review, we discuss the evidence for these interacting pathways and describe how the capacity of KIT, and other receptors, to influence FcepsilonRI-dependent mast-cell-mediator release might be a function of the relative abilities of these receptors to activate these alternative pathways.
Gilfillan
Alasdair M
AM
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C206, 10 Center Drive, MSC 1881, Bethesda, Maryland 20892-1881, USA. agilfillan@niaid.nih.gov
Tkaczyk
Christine
C
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D008407:Mast Cells / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D051966:Phospholipase C gamma / Q000378:metabolism; D010750:Phosphoproteins / Q000502:physiology; D010766:Phosphorylation; D017455:Receptors, IgE / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C110810:LAT protein, human; C419196:LAT2 protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D017455:Receptors, IgE; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D051966:Phospholipase C gamma