Plasma membranes (PMs) act as primary cellular checkpoints for sensing signals and controlling solute transport. Membrane proteins communicate with intracellular processes through protein interaction networks. Deciphering these signaling networks provides crucial information for elucidating in vivo cellular regulation. Large-scale proteomics enables system-wide characterization of the membrane proteome, identification of ligand–receptor pairs, and elucidation of signals originating at membranes. In this review we assess recent progress in the development of mass spectrometry (MS)-based proteomic pipelines for determining membrane signaling pathways. We focus in particular on current techniques for the analysis of membrane protein phosphorylation and interaction, and how these proteins may be connected to downstream changes in gene expression, metabolism, and physiology.

质膜（PMs）充当主要的细胞检查点，用于感应信号和控制溶质的运输。膜蛋白通过蛋白相互作用网络与细胞内过程进行通讯。对这些信号网络的解密为体内阐明提供了关键信息细胞调节。大规模蛋白质组学可以对膜蛋白组进行系统范围的表征，鉴定配体-受体对以及阐明源自膜的信号。在这篇综述中，我们评估了基于质谱（MS）的蛋白质组学管道在确定膜信号通路中的最新进展。我们特别关注当前用于分析膜蛋白磷酸化和相互作用的技术，以及这些蛋白如何与基因表达，代谢和生理学的下游变化联系起来。