The β‐arrestin proteins are key regulators of G protein‐coupled receptors, serving at least three distinct functions: inhibiting receptor signaling through G proteins, directing receptor trafficking from the cell surface after activation, and transmitting receptor‐initiated signals directly. How the two β‐arrestin proteins perform these many functions for hundreds of receptor types throughout the body, and specifically how β‐arrestin‐mediated signaling can be tuned to cellular conditions, remains an open question. Function‐based evidence and recent structure‐based evidence have suggested that patterns of receptor phosphorylation (“barcodes”) may be a critical determinant of β‐arrestin action. In this issue of EMBO Reports, Baidya and colleagues (Baidya et al, 2020a) report that specific receptor phosphorylation site clusters (“codes”) determine whether β‐arrestin 1 acts to promote or inhibit receptor activation of Erk mitogen‐activated protein kinases. They provide direct evidence for a functional barcode system by transferring inhibitory and stimulatory codes between receptors, suggesting future work to understand just how code site location in a receptor and its phosphorylation status can lead to very different functions of bound β‐arrestin proteins.

中文翻译：

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王国的钥匙：GPCR 磷酸化模式指导 β-抑制蛋白。

β-arrestin 蛋白是 G 蛋白偶联受体的关键调节因子，至少具有三个不同的功能：通过 G 蛋白抑制受体信号传导，激活后引导受体从细胞表面运输，以及直接传递受体引发的信号。这两种 β-arrestin 蛋白如何为全身数百种受体类型执行这么多功能，特别是如何将 β-arrestin 介导的信号调节到细胞条件，仍然是一个悬而未决的问题。基于功能的证据和最近基于结构的证据表明受体磷酸化模式（“条形码”）可能是 β-抑制蛋白作用的关键决定因素。在本期EMBO 报告中，Baidya 及其同事（Baidya等人, 2020a) 报告特定受体磷酸化位点簇（“代码”）决定了 β-抑制蛋白 1 是促进还是抑制 Erk 丝裂原活化蛋白激酶的受体激活。他们通过在受体之间转移抑制和刺激代码为功能性条形码系统提供了直接证据，这表明未来的工作要了解受体中的代码位点位置及其磷酸化状态如何导致结合的 β-抑制蛋白的功能非常不同。