Positive Regulation of T Cell Activation and Integrin Adhesion by the Adapter Fyb/Slap

作者：Emily K. Griffiths, Connie M. Krawczyk, Young‐Yun Kong, Monika Raab, Sharon J. Hyduk, Denis Bouchard, Vera S. F. Chan, I. Kozieradzki, Antonio Oliveira-dos-Santos, Andrew C. Wakeham, Pamela S. Ohashi, Myron I. Cybulsky, Christopher E. Rudd, Josef Martin Penninger · 发表于：Science · 年份：2001 · DOI：10.1126/science.1063397 · 被引用次数：285 · 研究领域：Cell Adhesion Molecules Research、T-cell and B-cell Immunology、Immune Cell Function and Interaction

The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial. We demonstrate that Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production in response to TCR stimulation. Fyb/Slap is also required in vivo for T cell-dependent immune responses. Functionally, Fyb/Slap has no apparent role in the activation of known TCR signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb/Slap regulates TCR-induced integrin clustering and adhesion. Thus, Fyb/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion.