Intrinsically Disordered Proteins Link Alternative Splicing and Post-translational Modifications to Complex Cell Signaling and Regulation

doi:10.1016/j.jmb.2018.03.028

	Intrinsically Disordered Proteins Link Alternative Splicing and Post-translational Modifications to Complex Cell Signaling and Regulation
	Zhou, Jianhong1 ; Zhao, Suwen1,2 ; Dunker, A. Keith 3
	2018-08-03
发表期刊	JOURNAL OF MOLECULAR BIOLOGY (IF:4.7[JCR-2023],4.9[5-Year])
ISSN	0022-2836
卷号	430 期号:16 页码:2342-2359
发表状态	已发表
DOI	10.1016/j.jmb.2018.03.028
摘要	Intrinsically disordered proteins and regions (IDPs and IDRs) lack well-defined tertiary structures, yet carry out various important cellular functions, especially those associated with cell signaling and regulation. In eukaryotes, IDPs and IDRs contain the preferred loci for both alternative splicing (AS) and many post-translational modifications (PTMs). Furthermore, AS and/or PTMs at these loci generally alter the signaling outcomes associated with these IDPs or IDRs, where the functional cooperation of these three features is named the IDP-AS-PTM toolkit. However, the prevalence of such functional modulations remains unknown. Also, the signal-altering mechanisms by which AS, and PTMs modulate function and the extent to which AS and PTMs collaborate in their signaling modulations have not been well defined for particular protein examples. Here we focus on three important signaling and regulatory IDR-containing protein families in humans, namely, G protein-coupled receptors (GPCRs), which are transmembrane proteins; the nuclear factors of activated T cells (NFATs), which are transcription factors; and the Src family kinases (SFKs), which are signaling enzymes. The goals here are to determine how AS and PTMs individually alter the outcomes of the signaling carried out by the various IDRs and to determine whether AS and PTMs work together to bring about differential cellular responses. We also present data indicating that a wide range of other signaling IDPs or IDRs undergo both AS- and PTM-based modifications, suggesting that they, too, likely take advantage of signal outcome modulations that result from collaboration between these two events. Hence, we propose that the widespread cooperation of IDPs, AS and/or PTMs provides an IDP-AS-PTM toolkit and substantially contributes to the vast complexity of eukaryotic cell signaling systems. (C) 2018 Elsevier Ltd. All rights reserved.
关键词	intrinsic disorder alternative splicing post-translational modification differential and context-dependent signaling signaling modulation and regulation
收录类别	SCI ; SCIE
语种	英语
资助项目	Science and Technology Commission of Shanghai Municipality[16ZR1448500]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000439402200007
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS关键词	TRANSCRIPTION FACTOR NFAT1 ; THROMBOXANE A(2) RECEPTOR ; SRC FAMILY ; COUPLED RECEPTORS ; FUNCTIONAL ANTHOLOGY ; POLYVALENT LIGAND ; PLASMA-MEMBRANE ; NITRIC-OXIDE ; GENE FAMILY ; DNA-BINDING
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/27382
专题	iHuman研究所_PI研究组_赵素文组生命科学与技术学院
通讯作者	Zhao, Suwen; Dunker, A. Keith
作者单位	1.ShanghaiTech Univ, iHuman Inst, 393 Huaxia Middle Rd, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Huaxia Middle Rd, Shanghai 201210, Peoples R China 3.Indiana Univ Sch Med, Dept Biochem & Mol Biol, Ctr Computat Biol & Bioinformat, 410 W 10th St,Suite 5000, Indianapolis, IN 46202 USA
第一作者单位	iHuman研究所
通讯作者单位	iHuman研究所; 生命科学与技术学院
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Zhou, Jianhong,Zhao, Suwen,Dunker, A. Keith. Intrinsically Disordered Proteins Link Alternative Splicing and Post-translational Modifications to Complex Cell Signaling and Regulation[J]. JOURNAL OF MOLECULAR BIOLOGY,2018,430(16):2342-2359.
APA	Zhou, Jianhong,Zhao, Suwen,&Dunker, A. Keith.(2018).Intrinsically Disordered Proteins Link Alternative Splicing and Post-translational Modifications to Complex Cell Signaling and Regulation.JOURNAL OF MOLECULAR BIOLOGY,430(16),2342-2359.
MLA	Zhou, Jianhong,et al."Intrinsically Disordered Proteins Link Alternative Splicing and Post-translational Modifications to Complex Cell Signaling and Regulation".JOURNAL OF MOLECULAR BIOLOGY 430.16(2018):2342-2359.