Open AccessAdaptor FYB (Fyn-binding protein) regulates integrin-mediated adhesion and mediator release: Differential involvement of the FYB SH3 domain
Author(s) -
Liping Geng,
Stefan M. Pfister,
Stine-Kathrein Kraeft,
Christopher E. Rudd
Publication year - 2001
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.191378198
Subject(s) - degranulation , fyn , microbiology and biotechnology , signal transducing adaptor protein , phosphorylation , tyrosine phosphorylation , integrin , mediator , proto oncogene tyrosine protein kinase src , sh3 domain , sh2 domain , biology , chemistry , receptor , biochemistry
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.