Identification of a novel human tankyrase through its interaction with the adaptor protein Grb14
Identification of a novel human tankyrase through its interaction with the adaptor protein Grb14
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DOI：
10.1074/jbc.m009756200
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发表时间：
2001-05-18
影响因子：
4.8
通讯作者：
Daly, RJ
中科院分区：
文献类型：
--
作者：
Lyons, RJ;Deane, R;Daly, RJ
端锚聚合酶是一种含有锚蛋白重复序列的聚（ADP-核糖）聚合酶，最初分离为端粒蛋白TRF 1的结合伴侣，但最近被鉴定为涉及高尔基体囊泡运输调控的有丝分裂原活化蛋白激酶底物。在这项研究中，一种新的人类端锚聚合酶，命名为端锚聚合酶2，分离在酵母双杂交筛选作为结合伴侣的Src同源2结构域的衔接蛋白Grb 14。端锚聚合酶2是一种分子量为130 kDa的蛋白质，其缺乏端锚聚合酶的N-末端组氨酸/脯氨酸/丝氨酸富集区，但含有相应的锚蛋白重复区、无菌α基序模块和聚（ADP-核糖）聚合酶同源结构域。TANKYRASE 2基因定位于染色体10q23.2并广泛表达，其中mRNA转录物在骨骼肌和胎盘中特别丰富。在亚细胞分级分离后，Grb 14和端锚聚合酶2都与低密度微粒体部分相关联，并且这些蛋白在体内的关联可以通过共免疫沉淀分析来检测。缺失分析表明Grb 14的N-末端110个氨基酸和端锚聚合酶2的锚蛋白重复序列10-19介导了这种相互作用。这项研究支持端锚聚合酶在细胞质信号转导途径中的作用，并表明囊泡运输可能参与Grb 14的亚细胞定位或信号功能。
Tankyrase is an ankyrin repeat-containing poly(ADP-ribose) polymerase originally isolated as a binding partner for the telomeric protein TRF1, but recently identified as a mitogen-activated protein kinase substrate implicated in regulation of Golgi vesicle trafficking. In this study, a novel human tankyrase, designated tankyrase 2, was isolated in a yeast two-hybrid screen as a binding partner for the Src homology 2 domain-containing adaptor protein Grb14. Tankyrase 2 is a 130-kDa protein, which lacks the N-terminal histidine/proline/serine-rich region of tankyrase, but contains a corresponding ankyrin repeat region, sterile alpha motif module, and poly(ADP-ribose) polymerase homology domain. The TANKYRASE 2 gene localizes to chromosome 10q23.2 and is widely expressed, with mRNA transcripts particularly abundant in skeletal muscle and placenta. Upon subcellular fractionation, both Grb14 and tankyrase 2 associate with the low density microsome fraction, and association of these proteins in vivo can be detected by co-immunoprecipitation analysis. Deletion analyses implicate the N-terminal 110 amino acids of Grb14 and ankyrin repeats 10-19 of tankyrase 2 in mediating this interaction, This study supports a role for the tankyrases in cytoplasmic signal transduction pathways and suggests that vesicle trafficking may be involved in the subcellular localization or signaling function of Grb14.