Adaptor FYB (Fyn-binding protein) regulates integrinmediated adhesion and mediator release: Differential involvement of the FYBSH3 domain

Aggregation of the high-affinity IgE receptor (Fc epsilon RI) on mast cells activates a tyrosine phosphorylation cascade that is required for adhesion and degranulation events leading to the release of histamine and other inf lammatory mediators. The full range of intracellular mediators that regulat e this process is unknown. Recent studies have identified a group of immune cell-specific adaptor proteins that include linker for activation of T-cel l (LAT), SH2-domain-containing leukocyte protein (SLP-76), and Fyn-T-bindin g protein (FYB)/SLP-76-associated protein (SLAP). In this study, we demonst rate 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 d omain in beta -hexosaminidase release, but not adhesion, and the up-regulat ion of mediator release by FYB in nonadherent cells. Fc epsilon RI aggregat ion increased FYB tyrosine phosphorylation, whereas confocal immunofluoresc ence microscopy showed that FYB colocalizes with Factin 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 p otential applications to inflammatory and allergic responses.