Cutting edge:: A novel function for the SLAP-130/FYB adapter protein in β1 integrin signaling and T lymphocyte migration

The role of integrin-mediated signaling events in T cell function remains incompletely characterized. We report here that alpha(4)beta(1) integrin stimulation of H9 T cells and normal human T cell blasts results in rapid and transient tyrosine phosphorylation of the adapter protein, SH2 domain-containing 76-kDa protein (SLP-76)-associated phosphoprotein of 130 kDa (SLAP-130)/FYB at levels comparable to those observed following TCR stimulation. Stimulation of T cells via the alpha(4)beta(1) integrin enhances the association of tyrosine phosphorylated SLAP-130/FYB with the SH2 domain of the src tyrosine kinase p59(fyn). Activation of normal T cells, but not H9 T cells, via alpha(4)beta(1) leads to tyrosine phosphorylation of SLP-76 as well as SLAP-130/FYB. Overexpression of SLAP-130/FYB in normal T cells enhances T cell migration through fibronectin-coated filters in response to the chemokine stromal cell-derived factor (SDF)-1 alpha. These results identify SLAP-130/FYB as a new tyrosine phosphorylated substrate in beta(1) integrin signaling and suggest a novel function for SLAP-130/FYB in regulating T lymphocyte motility.