Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec, Canada; Institute of Molecular Genetics of Montpellier (IGMM), Université de Montpellier, CNRS, Montpellier, France.
Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Trends Biochem Sci. 2024 Nov;49(11):986-999. doi: 10.1016/j.tibs.2024.08.004. Epub 2024 Sep 11.
Protein phosphorylation is a crucial regulatory mechanism in cell signaling, acting as a molecular switch that modulates protein function. Catalyzed by protein kinases and reversed by phosphoprotein phosphatases, it is essential in both normal physiological and pathological states. Recent advances have uncovered a vast and intricate landscape of protein phosphorylation that include histidine phosphorylation and more unconventional events, such as pyrophosphorylation and polyphosphorylation. Many questions remain about the true size of the phosphoproteome and, more importantly, its site-specific functional relevance. The involvement of unconventional actors such as pseudokinases and pseudophosphatases adds further complexity to be resolved. This review explores recent discoveries and ongoing challenges, highlighting the need for continued research to fully elucidate the roles and regulation of protein phosphorylation.
蛋白质磷酸化是细胞信号转导中至关重要的调节机制，作为一种分子开关，调节蛋白质的功能。它由蛋白激酶催化，由磷酸化蛋白磷酸酶逆转，在正常生理和病理状态下都是必不可少的。最近的研究揭示了一个广泛而复杂的蛋白质磷酸化景观，包括组氨酸磷酸化和更非常规的事件，如焦磷酸化和多磷酸化。关于磷酸蛋白质组的真实大小，以及更重要的是其特定部位的功能相关性，仍有许多问题有待解决。像假激酶和假磷酸酶这样的非常规因子的参与增加了需要解决的进一步复杂性。这篇综述探讨了最近的发现和正在面临的挑战，强调了需要继续研究以充分阐明蛋白质磷酸化的作用和调节。
