Characterization of PDZ-binding kinase, a mitotic kinase
Characterization of PDZ-binding kinase, a mitotic kinase
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DOI：
10.1073/pnas.090102397
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发表时间：
2000-05-09
影响因子：
11.1
通讯作者：
Lue, RA
中科院分区：
文献类型：
--
作者：
Gaudet, S;Branton, D;Lue, RA
hDlg是果蝇盘状大（Dlg）肿瘤抑制蛋白的人类同源物，已知其与肿瘤抑制蛋白APC和人乳头瘤病毒E6转化蛋白相互作用。在双杂交筛选中，我们鉴定了与hDlg的PDZ 2结构域结合的322-aa丝氨酸/苏氨酸激酶。这种PDZ结合激酶或PBK的mRNA在胎盘中最丰富，在成人脑组织中不存在。PBK的蛋白质序列具有所有特征性蛋白激酶亚结构域和C-末端PDZ结合T/SXV基序。在体外，PI 3 K通过其C-末端T/SXV基序特异性结合hDlg的PDZ 2。在HeLa细胞中，PI 3 K和hDlg在有丝分裂时被磷酸化，并且PI 3 K的有丝分裂磷酸化是其激酶活性所需的。在体外，cdc 2/cyclin B磷酸化PI 3 K。这一证据显示了PI 3 K如何将hDlg或其他含PDZ的蛋白质连接到调节细胞周期或细胞增殖的信号转导途径。
hDlg, the human homologue of the Drosophila Discs-large (Dlg) tumor suppressor protein, is known to interact with the tumor suppressor protein APC and the human papillomavirus E6 transforming protein. In a two-hybrid screen, we identified a 322-aa serine/threonine kinase that binds to the PDZ2 domain of hDlg. The mRNA for this PDZ-binding kinase, or PBK, is most abundant in placenta and absent from adult brain tissue. The protein sequence of PBK has all the characteristic protein kinase subdomains and a C-terminal PDZ-binding T/SXV motif. In vitro, PBK binds specifically to PDZ2 of hDlg through its C-terminal T/SXV motif. PBK and hDlg are phosphorylated at mitosis in HeLa cells, and the mitotic phosphorylation of PBK is required for its kinase activity. In vitro, cdc2/cyclin B phosphorylates PBK. This evidence shows how PBK could link hDlg or other PDZ-containing proteins to signal transduction pathways regulating the cell cycle or cellular proliferation.