Adaptor proteins play central roles in the assembly of molecular complexes and co-ordinated activation of specific pathways. Through their modular domain structure, the NCK family of adaptor proteins (NCK1 and NCK2) link protein targets via their single SRC Homology (SH) 2 and three SH3 domains. Classically, their SH2 domain binds to phosphotyrosine motif-containing receptors (e.g. receptor tyrosine kinases), while their SH3 domains bind polyproline motif-containing cytoplasmic effectors. Due to these functions being established for both NCK1 and NCK2, their roles were inaccurately assumed to be redundant. However, in contrast with this previously held view, NCK1 and NCK2 now have a growing list of paralog-specific functions, which underscores the need to further explore their differences. Here we review current evidence detailing how these two paralogs are unique, including differences in their gene/protein regulation, binding partners and overall contributions to cellular functions. To help explain these contrasting characteristics, we then discuss SH2/SH3 structural features, disordered interdomain linker regions and post-translational modifications. Together, this review seeks to highlight the importance of distinguishing NCK1 and NCK2 in research and to pave the way for investigations into the origins of their interaction specificity.

中文翻译：

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适应变化：解决 NCK1 和 NCK2 的动态和双重角色。


衔接蛋白在分子复合物的组装和特定通路的协调激活中起着核心作用。通过其模块化结构域结构，衔接蛋白 NCK 家族（NCK1 和 NCK2）通过其单个 SRC 同源 （SH） 2 和三个 SH3 结构域连接蛋白质靶标。通常，它们的 SH2 结构域与含有磷酸酪氨酸基序的受体（例如受体酪氨酸激酶）结合，而它们的 SH3 结构域与含有聚脯氨酸基序的细胞质效应子结合。由于这些功能是为 NCK1 和 NCK2 建立的，因此它们的作用被错误地假设为冗余。然而，与以前持有的观点相反，NCK1 和 NCK2 现在有越来越多的旁系同源物特异性函数列表，这强调了进一步探索它们差异的必要性。在这里，我们回顾了当前的证据，详细说明了这两种旁系同源物的独特之处，包括它们的基因/蛋白质调控、结合伴侣和对细胞功能的总体贡献的差异。为了帮助解释这些对比特征，我们随后讨论了 SH2/SH3 结构特征、无序的结构域间接头区域和翻译后修饰。总之，本综述旨在强调在研究中区分 NCK1 和 NCK2 的重要性，并为研究它们相互作用特异性的来源铺平道路。