Cutting Edge: A Novel Function for the SLAP-130/FYB Adapter Protein in β1 Integrin Signaling and T Lymphocyte Migration

作者：Anne Hunter, Nadine R. Ottoson, Nancy J. Boerth, Gary A. Koretzky, Yoji Shimizu · 发表于：The Journal of Immunology · 年份：2000 · DOI：10.4049/jimmunol.164.3.1143 · 被引用次数：78 · 研究领域：Cell Adhesion Molecules Research、T-cell and B-cell Immunology、Immune Response and Inflammation

The role of integrin-mediated signaling events in T cell function remains incompletely characterized. We report here that alpha4beta1 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 alpha4beta1 integrin enhances the association of tyrosine phosphorylated SLAP-130/FYB with the SH2 domain of the src tyrosine kinase p59fyn. Activation of normal T cells, but not H9 T cells, via alpha4beta1 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)-1alpha. These results identify SLAP-130/FYB as a new tyrosine phosphorylated substrate in beta1 integrin signaling and suggest a novel function for SLAP-130/FYB in regulating T lymphocyte motility.