Cdk5-mediated phosphorylation of CRMP-2 enhances its interaction with CaV2.2
Cdk5-mediated phosphorylation of CRMP-2 enhances its interaction with CaV2.2
复制标题
DOI：
10.1016/j.febslet.2012.09.022
复制
发表时间：
2012-11-02
期刊：
影响因子：
3.5
通讯作者：
Khanna, Rajesh
中科院分区：
文献类型：
--
作者：
Brittain, Joel M.;Wang, Yuying;Khanna, Rajesh
轴突/树突调节蛋白-2(CRMP-2)双向调节N型电压门控钙通道(Cav2.2)。但细胞周期蛋白依赖性激酶5(CDK5)介导的CRMP-2的磷酸化如何影响其与Cav2.2的相互作用和调控尚不清楚。CDK5磷酸化缺失的CRMP-2-S522A突变体或表达非活性CDK5的细胞均未观察到CRMP-2通过Cav2.2介导的电流增强。伴随着内源性CRMP2的下调和CRMP2-S522A突变体的高表达，而Rho激酶CRMP2-T555A突变体的作用不明显。CDK5磷酸化的CRMP-2与Cav2.2的相关性增加。这些结果证实了CDK5在CRMP2介导的Cav2.2调控中的重要作用。蛋白质相互作用结构概述：Gsk3b通过磷酸酶分析(View Interaction)磷酸化Crmp2(View Interaction)Crmp2通过反标签免疫共沉淀(View Interaction)与Cav2.2物理相互作用(C)2012欧洲生化学会联合会。爱思唯尔出版公司版权所有。
The axon/dendrite specification collapsin response mediator protein-2 (CRMP-2) bidirectionally regulates N-type voltage-gated Ca2+ channels (CaV2.2). But how cyclin dependent kinase 5 (Cdk5)-mediated phosphorylation of CRMP-2 affects its interaction/regulation with CaV2.2 is unknown. CRMP-2-mediated enhancement of currents via CaV2.2 was not observed with a Cdk5 phospho-null CRMP-2-S522A mutant or in cells expressing an inactive Cdk5. Concomitant knockdown of endogenous CRMP2 and overexpression of CRMP2-S522A mutant refractory to knockdown phenocopied the reduction in Ca2+ influx while the Rho kinase CRMP2-T555A mutant was ineffective. Cdk5-phosphorylated CRMP-2 had increased association with CaV2.2. These results identify an important role for Cdk5 in CRMP2-mediated CaV2.2 regulation.Structured summary of protein interactions:Gsk3b phosphorylates Crmp2by phosphatase assay (View interaction)Crmp2 physically interacts with Cav2.2 by anti tag coimmunoprecipitation (View interaction) (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.