Adaptor FYB (Fyn-binding protein) regulates integrin-mediated adhesion and mediator release: differential involvement of the FYB SH3 domain.
Aggregation of the high-affinity IgE receptor (FcepsilonRI) on mast cells activates a tyrosine phosphorylation cascade that is required for adhesion and degranulation events leading to the release of histamine and other inflammatory mediators. The full range of intracellular mediators that regulate this process is unknown. Recent studies have identified a group of immune cell-specific adaptor proteins that include linker for activation of T-cell (LAT), SH2-domain-containing leukocyte protein (SLP-76), and Fyn-T-binding protein (FYB)/SLP-76-associated protein (SLAP). In this study, we demonstrate that FYB can up-regulate integrin-mediated adhesion to fibronectin and mediator release in RBL-2H3 mast cells. The regulation of these two events could be distinguished from each other by the requirement of the FYB SH3 domain in beta-hexosaminidase release, but not adhesion, and the up-regulation of mediator release by FYB in nonadherent cells. FcepsilonRI aggregation increased FYB tyrosine phosphorylation, whereas confocal immunofluorescence microscopy showed that FYB colocalizes with F-actin in membrane ruffles and plaques. Our findings identify FYB as a regulator of integrin-mediated adhesion and degranulation events, which, in the case of mast cells, has potential applications to inflammatory and allergic responses.
Geng
L
L
Division of Tumor Immunology, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA 02115-6084, USA.
Pfister
S
S
Kraeft
S K
SK
Rudd
C E
CE
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology*; D003001:Cloning, Molecular; D005353:Fibronectins / Q000276:immunology; D006801:Humans; D016023:Integrins / Q000276:immunology*; D015759:Ionomycin / Q000494:pharmacology; D018613:Microscopy, Confocal; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C106957:FYB1 protein, human; D005353:Fibronectins; D016023:Integrins; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate