SPECIFIC ACTIVATION OF CDC25 TYROSINE PHOSPHATASES BY B-TYPE CYCLINS - EVIDENCE FOR MULTIPLE ROLES OF MITOTIC CYCLINS
SPECIFIC ACTIVATION OF CDC25 TYROSINE PHOSPHATASES BY B-TYPE CYCLINS - EVIDENCE FOR MULTIPLE ROLES OF MITOTIC CYCLINS
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DOI：
10.1016/0092-8674(91)90294-9
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发表时间：
1991-12-20
期刊：
影响因子：
64.5
通讯作者：
BEACH, D
中科院分区：
文献类型：
--
作者：
GALAKTIONOV, K;BEACH, D
两个先前未确定的人类cdc25基因cdc25A和cdc25B已被分离出来。这两种基因都挽救了裂变酵母的cdc25ts突变体。将抗cdc25a抗体微量注射到HeLa细胞中，使其在有丝分裂中停止。cdc25A和cdc25B显示内源性酪氨酸磷酸酶活性，在缺乏cdc2的情况下，通过化学计量添加周期蛋白B1或B2而不是A或D1，可以刺激其数倍。在HeLa细胞中检测到cdc25A和细胞周期蛋白B1/cdc2之间的关联。这些发现表明，b型细胞周期蛋白是一种多功能蛋白，不仅作为cdc2蛋白激酶的M期调控亚基，还可以激活cdc25酪氨酸磷酸酶，其中cdc2是其生理底物。在细胞周期蛋白和酪氨酸PTPases之间发现了一个氨基酸相似性区域。该区域在cdc25磷酸酶中不存在。该基序可能代表了cdc25与细胞周期蛋白B分子间相互作用的激活域。
Two previously unidentified human cdc25 genes have been isolated, cdc25A and cdc25B. Both genes rescue a cdc25ts mutant of fission yeast. Microinjection of anti-cdc25A antibodies into HeLa cells causes their arrest in mitosis. cdc25A and cdc25B display endogenous tyrosine phosphatase activity that is stimulated several-fold, in the absence of cdc2, by stoichiometric addition of either cyclin B1 or B2 but not A or D1. Association between cdc25A and cyclin B1/cdc2 was detected in the HeLa cells. These findings indicate that B-type cyclins are multifunctional proteins that not only act as M phase regulatory subunits of the cdc2 protein kinase, but also activate the cdc25 tyrosine phosphatase, of which cdc2 is the physiological substrate. A region of amino acid similarity between cyclins and tyrosine PTPases has been detected. This region is absent in cdc25 phosphatases. The motif may represent an activating domain that has to be provided to cdc25 by intermolecular interaction with cyclin B.