Intrinsically disordered proteins play diverse roles in cell signaling

Cell Communication and Signaling

A. Keith Dunker¹  Vladimir N. Uversky²  Sarah E. Bondos³ 

[1] Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, 33612, Tampa, FL, USA;Institute for Biological Instrumentation of the Russian Academy of Sciences, Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, 142290, Pushchino, Moscow Region, Russia;Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, 77843, College Station, TX, USA;

关键词: Cell signal amplification;    Integration;    Differentiation;    Propagation;    Specificity;   

DOI  :  10.1186/s12964-022-00821-7

来源: Springer

【 摘 要 】

Signaling pathways allow cells to detect and respond to a wide variety of chemical (e.g. Ca2+ or chemokine proteins) and physical stimuli (e.g., sheer stress, light). Together, these pathways form an extensive communication network that regulates basic cell activities and coordinates the function of multiple cells or tissues. The process of cell signaling imposes many demands on the proteins that comprise these pathways, including the abilities to form active and inactive states, and to engage in multiple protein interactions. Furthermore, successful signaling often requires amplifying the signal, regulating or tuning the response to the signal, combining information sourced from multiple pathways, all while ensuring fidelity of the process. This sensitivity, adaptability, and tunability are possible, in part, due to the inclusion of intrinsically disordered regions in many proteins involved in cell signaling. The goal of this collection is to highlight the many roles of intrinsic disorder in cell signaling. Following an overview of resources that can be used to study intrinsically disordered proteins, this review highlights the critical role of intrinsically disordered proteins for signaling in widely diverse organisms (animals, plants, bacteria, fungi), in every category of cell signaling pathway (autocrine, juxtacrine, intracrine, paracrine, and endocrine) and at each stage (ligand, receptor, transducer, effector, terminator) in the cell signaling process. Thus, a cell signaling pathway cannot be fully described without understanding how intrinsically disordered protein regions contribute to its function. The ubiquitous presence of intrinsic disorder in different stages of diverse cell signaling pathways suggest that more mechanisms by which disorder modulates intra- and inter-cell signals remain to be discovered.Graphical abstract

【 授权许可】

CC BY