Griffiths E K, Krawczyk C, Kong Y Y, Raab M, Hyduk S J, Bouchard D, Chan V S, Kozieradzki I, Oliveira-Dos-Santos A J, Wakeham A, Ohashi P S, Cybulsky M I, Rudd C E, Penninger J M
Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1.
Science. 2001 Sep 21;293(5538):2260-3. doi: 10.1126/science.1063397.
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.
分子衔接蛋白Fyb/Slap调节T细胞受体（TCR）下游的信号传导，但其发挥的是正向还是负向作用仍存在争议。我们证明，Fyb/Slap缺陷型T细胞在对TCR刺激的应答中表现出增殖缺陷和细胞因子产生缺陷。在体内，T细胞依赖性免疫反应也需要Fyb/Slap。在功能上，Fyb/Slap在已知的TCR信号通路激活、F-肌动蛋白聚合或TCR聚集方面没有明显作用。相反，Fyb/Slap调节TCR诱导的整合素聚集和黏附。因此，Fyb/Slap是首个被鉴定出的将TCR刺激与调控T细胞黏附的整合素亲和力调节相偶联的分子衔接蛋白。
