PP2A-B' holoenzyme substrate recognition, regulation and role in cytokinesis.
PP2A-B' holoenzyme substrate recognition, regulation and role in cytokinesis.
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DOI：
10.1038/celldisc.2017.27
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发表时间：
2017
期刊：
影响因子：
33.5
通讯作者：
Xing Y
中科院分区：
文献类型：
--
作者：
Wu CG;Chen H;Guo F;Yadav VK;Mcilwain SJ;Rowse M;Choudhary A;Lin Z;Li Y;Gu T;Zheng A;Xu Q;Lee W;Resch E;Johnson B;Day J;Ge Y;Ong IM;Burkard ME;Ivarsson Y;Xing Y
蛋白磷酸酶2A（PP 2A）是一种主要的丝氨酸/苏氨酸磷酸酶;它形成多种异源三聚体全酶，抵消激酶的作用。使用一个肽组，瓷砖的人类蛋白质组的无序区域，我们确定了蛋白质含有[LMFI]xx[ILV]xEx基序，作为B′-家族PP 2A调节亚基和全酶的相互作用位点。B′结合基序在底物识别和底物结合的竞争性抑制中具有重要作用。通过对100多个新的配体的鉴定，我们证实了最近发现的LxxIxEx B′α结合基序是B′亚基的共同结合位点，且基序的2、7、8和9位的S/T磷酸化或D/E残基可增强相互作用。在人类蛋白质组中，数百种蛋白质具有内在的或磷酸化响应的B′相互作用基序，并定位于不同的细胞器，如中间体，预测激酶促进的PP 2A-B ′全酶的募集，以在有丝分裂和胞质分裂中严格控制磷酸化的时空。此外，Polo样激酶1介导的Cyk 4/RACGAP 1磷酸化，一种位于中间体的中心纺锤体成分，促进RhoA鸟嘌呤核苷酸交换因子（上皮细胞转化序列2（Ect 2））和PP 2A-B ′的结合，进而使Cyk 4去磷酸化并破坏Ect 2结合。这个反馈信号环精确地控制RhoA激活，并指定一个限制性区域用于卵裂沟内移。我们的研究结果为进一步研究PP 2A-B ′全酶在各种细胞过程中形成的不同信号通路提供了框架。
Protein phosphatase 2A (PP2A) is a major Ser/Thr phosphatase; it forms diverse heterotrimeric holoenzymes that counteract kinase actions. Using a peptidome that tiles the disordered regions of the human proteome, we identified proteins containing [LMFI]xx[ILV]xEx motifs that serve as interaction sites for B′-family PP2A regulatory subunits and holoenzymes. The B′-binding motifs have important roles in substrate recognition and in competitive inhibition of substrate binding. With more than 100 novel ligands identified, we confirmed that the recently identified LxxIxEx B′α-binding motifs serve as common binding sites for B′ subunits with minor variations, and that S/T phosphorylation or D/E residues at positions 2, 7, 8 and 9 of the motifs reinforce interactions. Hundreds of proteins in the human proteome harbor intrinsic or phosphorylation-responsive B′-interaction motifs, and localize at distinct cellular organelles, such as midbody, predicting kinase-facilitated recruitment of PP2A-B′ holoenzymes for tight spatiotemporal control of phosphorylation at mitosis and cytokinesis. Moroever, Polo-like kinase 1-mediated phosphorylation of Cyk4/RACGAP1, a centralspindlin component at the midbody, facilitates binding of both RhoA guanine nucleotide exchange factor (epithelial cell transforming sequence 2 (Ect2)) and PP2A-B′ that in turn dephosphorylates Cyk4 and disrupts Ect2 binding. This feedback signaling loop precisely controls RhoA activation and specifies a restricted region for cleavage furrow ingression. Our results provide a framework for further investigation of diverse signaling circuits formed by PP2A-B′ holoenzymes in various cellular processes.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
7.3
作者：
Alexander J;Lim D;Joughin BA;Hegemann B;Hutchins JR;Ehrenberger T;Ivins F;Sessa F;Hudecz O;Nigg EA;Fry AM;Musacchio A;Stukenberg PT;Mechtler K;Peters JM;Smerdon SJ;Yaffe MB
通讯作者：
Yaffe MB
DOI：
10.1186/s12964-015-0116-8
发表时间：
2015-08-22
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Blikstad C;Ivarsson Y
通讯作者：
Ivarsson Y
影响因子：
50.3
作者：
Chen, W;Possemato, R;Hahn, WC
通讯作者：
Hahn, WC
影响因子：
14.9
作者：
Hornbeck PV;Kornhauser JM;Tkachev S;Zhang B;Skrzypek E;Murray B;Latham V;Sullivan M
通讯作者：
Sullivan M