β-arrestin1激活JNK信号通路促进慢性髓细胞白血病细胞K562增殖  

β-arrestin1 promotes chronic myeloid leukemia cell proliferation by activating JNK signaling pathway

作　　者：陈卉[1] 李康[1] 王毅[1] 谭正兰 邹琳[1] 

机构地区：[1]重庆医科大学附属儿童医院临床分子医学中心//儿童发育疾病研究教育部重点实验室//儿科学重庆市重点实验室//重庆市儿童发育重大疾病诊治与预防国际科技合作基地,四川重庆400014

出　　处：《南方医科大学学报》2015年第5期677-681,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(81373444)~~

摘　　要：目的以CML K562细胞为研究对象,探索β-arrestin1促进CML细胞增殖的相关信号通路。方法以β-arrestin1慢病毒载体感染CML K562细胞,形成稳定的K562-siβ1和K562-β1细胞,及非特异性si RNA对照K562-Ctrl细胞。以此为研究对象,利用细胞计数与CCK-8实验检测细胞增殖能力;Western blot检测蛋白表达;免疫共沉淀(Co-IP)实验检测蛋白间的相互作用。结果细胞计数与CCK-8实验结果显示K562-β1细胞增殖与细胞存活率能力显著高于K562-Ctrl,而K562-siβ1显著低于K562-Ctrl。Western blot结果表明β-arrestin1特异性增强磷酸化JNK表达,JNK抑制剂SP600125能抑制p-JNK表达和K562细胞增殖;免疫共沉淀实验表明β-arrestin1能与Src结合。结论 CML K562细胞中β-arrestin1与Src结合,促进JNK信号通路激活,从而促进细胞增殖。Objective To investigate the signaling pathways involved inβ-arrestin1-induced proliferation of K562 cells. Methods We established stable cell lines K562-siβ1 and K562-β1 by lentivirus-mediated β-arrestin1 knock-down or overexpression in K562 cells, with cells transfected with non-specific siRNA as the control （K562-Ctrl）. The proliferation of these cells were evaluated by cell counting and CCK-8 assays. Western blotting was used to detect the expression of JNK and p-JNK in the cells, and co-immunoprecipitation （Co-IP） assay was employed to investigate the interaction between β-arrestin1 and Src. Results K562-β1 cells showed significantly greater but K562-siβ1 cells had significantly lower proliferation ability and cell survival rate than K562-Ctrl cells. Western blotting showed thatβ-arrestin1 specifically enhanced the expression of p-JNK, and the JNK inhibitor SP600125 obviously suppressed p-JNK and cell proliferation of K562 cells. Co-IP assay revealed the binding ofβ-arrestin1 to Src. Conclusions In K562 cells,β-arrestin1 activates JNK signaling pathway by binding to Src to promote the cell proliferation.

关 键 词：β-arrestin1 CML 细胞增殖 JNK 

分 类 号：R733.72[医药卫生—肿瘤]