The scaffold protein IQGAP1 assembles multiprotein signaling complexes to influence biological functions. Cell surface receptors, particularly receptor tyrosine kinases and G-protein coupled receptors, are common IQGAP1 binding partners. Interactions with IQGAP1 modulate receptor expression, activation, and/or trafficking. Moreover, IQGAP1 couples extracellular stimuli to intracellular outcomes via scaffolding of signaling proteins downstream of activated receptors, including mitogen-activated protein kinases, constituents of the phosphatidylinositol 3-kinase pathway, small GTPases, and β-arrestins. Reciprocally, some receptors influence IQGAP1 expression, subcellular localization, binding properties, and post-translational modifications. Importantly, the receptor:IQGAP1 crosstalk has pathological implications ranging from diabetes and macular degeneration to carcinogenesis. Here, we describe the interactions of IQGAP1 with receptors, summarize how they modulate signaling, and discuss their contribution to pathology. We also address the emerging functions in receptor signaling of IQGAP2 and IQGAP3, the other human IQGAP proteins. Overall, this review emphasizes the fundamental roles of IQGAPs in coupling activated receptors to cellular homeostasis.

中文翻译：

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IQGAP 支架：桥接受体激活与细胞信号传导的关键节点

支架蛋白 IQGAP1 组装多蛋白信号复合物以影响生物功能。细胞表面受体，特别是受体酪氨酸激酶和 G 蛋白偶联受体，是常见的 IQGAP1 结合伴侣。与 IQGAP1 的相互作用调节受体表达、激活和/或运输。此外，IQGAP1通过激活受体下游信号蛋白的支架将细胞外刺激与细胞内结果耦合起来，这些信号蛋白包括丝裂原激活蛋白激酶、磷脂酰肌醇3激酶途径的成分、小GTP酶和β-抑制蛋白。相反，一些受体影响 IQGAP1 表达、亚细胞定位、结合特性和翻译后修饰。重要的是，受体：IQGAP1 串扰具有从糖尿病、黄斑变性到致癌的病理学影响。在这里，我们描述了 IQGAP1 与受体的相互作用，总结了它们如何调节信号传导，并讨论了它们对病理学的贡献。我们还探讨了 IQGAP2 和 IQGAP3（其他人类 IQGAP 蛋白）受体信号传导中的新兴功能。总的来说，这篇综述强调了 IQGAP 在耦合激活受体与细胞稳态方面的基本作用。