Roles of adaptor molecules in mast cell activation.
The release of pro-inflammatory mediators from mast cells generally occurs following antigen-dependent aggregation of the high-affinity receptors for IgE (FcepsilonRI) expressed on the cell surface. Under the appropriate conditions, however, other receptors including the high-affinity receptor for IgG (FcgammaRI), Kit, the C3a complement component receptor, and adenosine receptors, can also induce or potentiate mast cell activation. In contrast, receptors such as the FcgammaRIIb low-affinity IgG receptor, and gp49b, when co-ligated with FcepsilonRI, down-regulate mast cell activation. The driving force by which the FcepsilonRI, the FcgammaRI, Kit, and potentially other receptors, lead to mast cell degranulation, arachidonic acid metabolism and cytokine gene expression, is a series of tyrosine kinase-mediated protein phosphorylation events which result in recruitment and subsequent activation of signaling enzymes. Similar processes are required by gp49b and FcgammaRIIb for the down-regulation of mast cell activation. The cellular localization and sequence of these events, the subsequent amplification and diversification of the signaling cascade, and potentially, the termination of these events, are regulated by an important group of signaling proteins termed adaptor molecules. In this chapter, we discuss the structure and properties of these molecules and how these proteins regulate the cellular processes associated with receptor-mediated mast cell activation.
Tkaczyk
Christine
C
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md., USA.
Iwaki
Shoko
S
Metcalfe
Dean D
DD
Gilfillan
Alasdair M
AM
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D046912:Multiprotein Complexes; D011485:Protein Binding; D017455:Receptors, IgE / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D046912:Multiprotein Complexes; D017455:Receptors, IgE; D017452:Receptors, IgG