Department of Evolutionary Biology, University of Siena, Siena, Italy.
FEBS Lett. 2010 Dec 15;584(24):4915-22. doi: 10.1016/j.febslet.2010.08.046. Epub 2010 Sep 7.
Protein adapters couple surface receptors to multiple intracellular signaling modules by acting as scaffolds for the assembly of multimolecular complexes responsible for the coordination and amplification of signals. Through the spatiotemporally controlled recruitment of mediators with opposite activities (e.g. protein tyrosine kinases and phosphatases), adapters are implicated not only in signal initiation and propagation, but also in feedback loops for signal extinction. Moreover, adaptors specialized in preventing or dampening signaling have been more recently discovered. Here we shall present of brief overview of the principal adaptors which act as negative regulators of TCR and BCR signaling, with a focus of the mechanisms underlying this function. We shall then discuss our recent findings implicating p66Shc and Rai, two members of the Shc family of cytosolic protein adapters, in the negative control of antigen receptor signaling, and their role as gatekeepers of autoimmunity and leukemia.
蛋白质衔接子通过充当多分子复合物组装的支架，将表面受体与多个细胞内信号模块偶联，这些复合物负责协调和放大信号。通过时空控制募集具有相反活性的介质（例如蛋白酪氨酸激酶和磷酸酶），衔接子不仅参与信号的起始和传播，而且参与信号衰减的反馈回路。此外，最近发现了专门用于预防或抑制信号传递的衔接子。在这里，我们将简要概述作为 TCR 和 BCR 信号负调节剂的主要衔接子，重点介绍其功能的机制。然后，我们将讨论我们最近的发现，表明 Shc 家族细胞质蛋白衔接子的两个成员 p66Shc 和 Rai，参与了抗原受体信号的负调控，以及它们作为自身免疫和白血病的“门卫”的作用。
