Cell Biology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; MRC Laboratory for Molecular Cell Biology, University College London, Gower St., London WC1E 6BT, UK.
Cell Biology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cancer Research UK (CRUK) Beatson Institute, University of Glasgow, Bearsden, Glasgow G61 1BD, UK.
Dev Cell. 2019 Feb 25;48(4):491-505.e9. doi: 10.1016/j.devcel.2018.12.001. Epub 2019 Jan 3.
Signaling from chemoattractant receptors activates the cytoskeleton of crawling cells for chemotaxis. We show using phosphoproteomics that different chemoattractants cause phosphorylation of the same core set of around 80 proteins in Dictyostelium cells. Strikingly, the majority of these are phosphorylated at an [S/T]PR motif by the atypical MAP kinase ErkB. Unlike most chemotactic responses, ErkB phosphorylations are persistent and do not adapt to sustained stimulation with chemoattractant. ErkB integrates dynamic autophosphorylation with chemotactic signaling through G-protein-coupled receptors. Downstream, our phosphoproteomics data define a broad panel of regulators of chemotaxis. Surprisingly, targets are almost exclusively other signaling proteins, rather than cytoskeletal components, revealing ErkB as a regulator of regulators rather than acting directly on the motility machinery. ErkB null cells migrate slowly and orientate poorly over broad dynamic ranges of chemoattractant. Our data indicate a central role for ErkB and its substrates in directing chemotaxis.
趋化因子受体发出的信号激活了爬行细胞的细胞骨架，以进行趋化运动。我们使用磷酸蛋白质组学表明，不同的趋化因子会导致盘基网柄菌细胞中约 80 种核心蛋白的磷酸化。引人注目的是，这些蛋白中的大多数都被非典型 MAP 激酶 ErkB 在 [S/T]PR 基序上磷酸化。与大多数趋化反应不同，ErkB 磷酸化是持久的，不会适应持续的趋化刺激。ErkB 通过 G 蛋白偶联受体将动态自身磷酸化与趋化信号整合在一起。在下游，我们的磷酸蛋白质组学数据定义了一个广泛的趋化调节因子面板。令人惊讶的是，靶点几乎都是其他信号蛋白，而不是细胞骨架成分，这表明 ErkB 是调节因子的调节剂，而不是直接作用于运动机制。ErkB 缺失细胞在广泛的趋化剂动态范围内迁移缓慢且定向不良。我们的数据表明 ErkB 及其底物在指导趋化作用中起着核心作用。
