Human mob proteins regulate the NDR1 and NDR2 serine-threonine kinases
Human mob proteins regulate the NDR1 and NDR2 serine-threonine kinases
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DOI：
10.1074/jbc.m401999200
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发表时间：
2004-06-04
影响因子：
4.8
通讯作者：
Silver, PA
中科院分区：
文献类型：
--
作者：
Devroe, E;Erdjument-Bromage, H;Silver, PA
人NDR 1（核Dbf 2相关）是一种广泛表达的核丝氨酸-苏氨酸激酶，与细胞增殖和/或肿瘤进展有关。在这里，我们提出了人类NDR 2丝氨酸-苏氨酸激酶的分子特征，它与NDR 1有87%的序列同一性。NDR 2在大多数人体组织中表达，在胸腺中表达最高。与NDR 1相反，NDR 2被排除在细胞核之外，并表现出点状细胞质分布。NDR 1和NDR 2的差异定位表明每个激酶可能具有不同的功能。因此，为了鉴定与NDR 1或NDR 2相互作用的蛋白质，从Jurkat T细胞免疫沉淀表位标记的激酶。鉴定出两种与酿酒酵母激酶调节剂Mob 1和Mob 2同源的未表征蛋白质。我们证明，NDR 1和NDR 2部分共定位与人Mob 2在HeLa细胞中，并确认NDR-Mob在细胞提取物中的相互作用。有趣的是，NDR 1和NDR 2与Mob 2形成稳定的复合物，这种结合极大地刺激了NDR 1和NDR 2的催化活性。总之，这项工作确定了一类独特的人类激酶激活亚基，可能在功能上类似于细胞周期蛋白。
Human NDR1 (nuclear Dbf2-related) is a widely expressed nuclear serine-threonine kinase that has been implicated in cell proliferation and/or tumor progression. Here we present molecular characterization of the human NDR2 serine-threonine kinase, which shares similar to87% sequence identity with NDR1. NDR2 is expressed in most human tissues with the highest expression in the thymus. In contrast to NDR1, NDR2 is excluded from the nucleus and exhibits a punctate cytoplasmic distribution. The differential localization of NDR1 and NDR2 suggests that each kinase may serve distinct functions. Thus, to identify proteins that interact with NDR1 or NDR2, epitope-tagged kinases were immunoprecipitated from Jurkat T-cells. Two uncharacterized proteins that are homologous to the Saccharomyces cerevisiae kinase regulators Mob1 and Mob2 were identified. We demonstrate that NDR1 and NDR2 partially colocalize with human Mob2 in HeLa cells and confirm the NDR-Mob interactions in cell extracts. Interestingly, NDR1 and NDR2 form stable complexes with Mob2, and this association dramatically stimulates NDR1 and NDR2 catalytic activity. In summary, this work identifies a unique class of human kinase-activating subunits that may be functionally analagous to cyclins.