Simeoni Luca, Lindquist Jonathan A, Smida Michal, Witte Vanessa, Arndt Boerge, Schraven Burkhart
Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Magdeburg, Germany.
Immunol Rev. 2008 Aug;224:215-28. doi: 10.1111/j.1600-065X.2008.00656.x.
Signals emanating from antigen receptors critically regulate immune cell activation, survival, and differentiation. Transmembrane adapter proteins (TRAPs), a group of molecules that organize signaling complexes at the plasma membrane, play a pivotal role in propagating and fine-tuning antigen receptor-mediated signaling. During the last years, it has been demonstrated that most of the TRAPs possess inhibitory functions, including linker for activation of T cells (LAT), the best characterized adapter that links the T-cell receptor (TCR) to Ca(2+) flux and mitogen-activated protein kinase activation. Indeed, it appears that LAT may assemble inhibitory complexes that trigger negative feedback loops, thus terminating T-cell activation. Additionally, recent data demonstrate that SIT [Src homology 2 domain-containing phosphatase 2 (SHP2)-interacting TRAP] fine-tunes TCR-mediated signaling events and negatively regulates T-cell development and homeostasis. The experimental evidence suggests that TRAPs play a crucial role also in establishing tolerance. In fact, loss of SIT, LAX, or NTAL (non-T cell activation linker)/linker for activation of B cells (LAB) resulted in the spontaneous development of autoimmune diseases. Moreover, we recently showed that in addition to the inhibition of Src-family kinases, PAG (phosphoprotein associated with glycosphingolipid-enriched domains) is also involved in the negative regulation of Ras activation. Collectively, these data demonstrate that TRAPs are important modulators of immune cell activation and function. Finally, it appears that TRAPs possess redundant yet not completely overlapping functions.
来自抗原受体的信号对免疫细胞的激活、存活和分化起着关键的调节作用。跨膜衔接蛋白（TRAPs）是一类在质膜上组织信号复合物的分子，在传播和微调抗原受体介导的信号中起关键作用。在过去几年中，已证明大多数TRAPs具有抑制功能，包括T细胞激活连接蛋白（LAT），它是将T细胞受体（TCR）与Ca(2+) 内流和丝裂原活化蛋白激酶激活相连接的特征最明确的衔接蛋白。事实上，LAT似乎可以组装抑制性复合物，触发负反馈回路，从而终止T细胞激活。此外，最近的数据表明，含Src同源2结构域的磷酸酶2（SHP2）相互作用的TRAP（SIT）可微调TCR介导的信号事件，并对T细胞发育和稳态起负调节作用。实验证据表明，TRAPs在建立免疫耐受方面也起着关键作用。实际上，SIT、LAX或非T细胞激活连接蛋白（NTAL）/B细胞激活连接蛋白（LAB）缺失会导致自身免疫性疾病的自发发展。此外，我们最近发现，除了抑制Src家族激酶外，与富含糖鞘脂结构域相关的磷蛋白（PAG）也参与Ras激活的负调节。总的来说，这些数据表明TRAPs是免疫细胞激活和功能的重要调节因子。最后，TRAPs似乎具有冗余但并非完全重叠的功能。
