THE 25-KDA FK506-BINDING PROTEIN IS LOCALIZED IN THE NUCLEUS AND ASSOCIATES WITH CASEIN KINASE-II AND NUCLEOLIN
THE 25-KDA FK506-BINDING PROTEIN IS LOCALIZED IN THE NUCLEUS AND ASSOCIATES WITH CASEIN KINASE-II AND NUCLEOLIN
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DOI：
10.1073/pnas.90.16.7769
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发表时间：
1993-08-15
影响因子：
11.1
通讯作者：
BURAKOFF, SJ
中科院分区：
文献类型：
--
作者：
JIN, YJ;BURAKOFF, SJ
FK 506结合蛋白（FKBP）已被确定为免疫抑制药物FK 506和雷帕霉素的细胞受体。最近，我们克隆了一个25-kDa的FKBP家族成员（FKBP 25），发现FKBP 25含有一个核定位序列和几个潜在的酪蛋白激酶II磷酸化位点。先前已经表明，酪蛋白激酶II对蛋白质的磷酸化可以增强它们的核定位。在这里，我们表明，FKBP 25是本地化的细胞核和谷胱甘肽S-转移酶融合蛋白FKBP 25（GST-FKBP 25）可以磷酸化酪蛋白激酶II。当GST-FKBP 25融合蛋白与纯化的酪蛋白激酶II或细胞裂解物一起孵育时，也形成稳定的FKBP 25/酪蛋白激酶II复合物。此外，当GST-FKBP 25与核裂解物一起孵育时，发现核仁素（酪蛋白激酶II的主要核底物）与GST-FKBP 25/酪蛋白激酶II复合物相关。酪蛋白激酶II磷酸化的几个胞质和核底物，包括核仁素，似乎是重要的细胞生长的调节。FKBP 25与酪蛋白激酶II的相互作用可能调节这些功能。
FK506-binding proteins (FKBPs) have been identified as the cellular receptors of the immunosuppressive drugs FK506 and rapamycin. Recently, we cloned a 25-kDa FKBP family member (FKBP25) and found that FKBP25 contains a nuclear localization sequence and several potential casein kinase II phosphorylation sites. It has been previously shown that phosphorylation of proteins by casein kinase II can enhance their nuclear localization. Here we demonstrate that FKBP25 is localized to the nucleus and that a glutathione S-transferase fusion protein of FKBP25 (GST-FKBP25) can be phosphorylated by casein kinase II. Also a stable FKBP25/casein kinase II complex was formed when the GST-FKBP25 fusion protein was incubated either with purified casein kinase II or with cell lysates. Furthermore, when GST-FKBP25 was incubated with nuclear lysates, nucleolin, a major nuclear substrate of casein kinase II, was found associated with the GST-FKBP25/casein kinase II complex. Casein kinase II phosphorylation of several cytosolic and nuclear substrates, including nucleolin, appears to be important for the regulation of cell growth. The interaction of FKBP25 with casein kinase II may regulate these functions.