Function, regulation and pathological roles of the Gab/DOS docking proteins.
Function, regulation and pathological roles of the Gab/DOS docking proteins.
复制标题
DOI：
10.1186/1478-811x-7-22
复制
发表时间：
2009-09-08
期刊：
影响因子：
--
通讯作者：
Brummer T
中科院分区：
文献类型：
--
作者：
Wöhrle FU;Daly RJ;Brummer T
自从十多年前被发现以来，Gab/DOS家族的对接蛋白已经成为后生动物中重要的信号元件。Gab/DOS蛋白整合和放大来自多种来源的信号，包括生长因子、细胞因子和抗原受体以及细胞粘附分子。它们还通过将信息从激活的受体引导到具有不同生物功能的信号通路，从而促进信号多样化。蛋白质生物化学和系统生物学的最新研究表明，Gab蛋白受前馈和反馈磷酸化事件以及蛋白质-蛋白质相互作用的复杂调控。因此，Gab/DOS对接蛋白是整个信号子系统的中心，在许多生理过程中发挥着重要的作用。此外，从各种形式的肿瘤到阿尔茨海默病，Gab蛋白的异常信号越来越多地与人类疾病联系在一起。本文就Gab/DOS家族的结构、效应功能、调控及其演变进行了综述。我们还总结了最近的发现暗示gabb蛋白，特别是Gab2亚型，在白血病，实体肿瘤和其他人类疾病。
Since their discovery a little more than a decade ago, the docking proteins of the Gab/DOS family have emerged as important signalling elements in metazoans. Gab/DOS proteins integrate and amplify signals from a wide variety of sources including growth factor, cytokine and antigen receptors as well as cell adhesion molecules. They also contribute to signal diversification by channelling the information from activated receptors into signalling pathways with distinct biological functions. Recent approaches in protein biochemistry and systems biology have revealed that Gab proteins are subject to complex regulation by feed-forward and feedback phosphorylation events as well as protein-protein interactions. Thus, Gab/DOS docking proteins are at the centre of entire signalling subsystems and fulfil an important if not essential role in many physiological processes. Furthermore, aberrant signalling by Gab proteins has been increasingly linked to human diseases from various forms of neoplasia to Alzheimer's disease. In this review, we provide a detailed overview of the structure, effector functions, regulation and evolution of the Gab/DOS family. We also summarize recent findings implicating Gab proteins, in particular the Gab2 isoform, in leukaemia, solid tumours and other human diseases.