FKBP12-rapamycin-associated protein or mammalian target of rapamycin (FRAP/mTOR) localization in the endoplasmic reticulum and the Golgi

FKBP12-rapamycin-associated protein or mammalian target of rapamycin (FRAP/mTOR) localization in the endoplasmic reticulum and the Golgi
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DOI:
10.1074/jbc.m305912200
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发表时间:
2004-01-02
影响因子:
4.8
通讯作者:
Zheng, XFS
Zheng, XFS
中科院分区:
生物学2区
文献类型:
--
作者:
Drenan, RM;Liu, XY;Zheng, XFS

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FKBP 12-雷帕霉素相关蛋白(FRAP)或哺乳动物雷帕霉素靶蛋白(mTOR)及其效应蛋白形成调节真核细胞生长和增殖的关键信号通路。虽然在这一途径中的蛋白质组分已开始被确定,很少有人知道他们的亚细胞定位或其定位的生理意义。通过免疫荧光,我们发现内源性和重组FRAP/mTOR蛋白主要定位于内质网(ER)和高尔基体。与这一发现相一致,FRAP/mTOR与钙连接蛋白(一种ER标记蛋白)共分馏。生化特性表明,FRAP/mTOR是一个外周ER/高尔基体蛋白与紧密的膜协会。最后,我们已经确定了FRAP/mTOR的结构域,这可能介导其与ER和高尔基体的关联。
FKBP12-rapamycin-associated protein ( FRAP) or mammalian target of rapamycin ( mTOR) and its effector proteins form a critical signaling pathway that regulates eukaryotic cell growth and proliferation. Although the protein components in this pathway have begun to be identified, little is known about their subcellular localization or the physiological significance of their localization. By immunofluorescence, we find that both endogenous and recombinant FRAP/mTOR proteins show localization predominantly in the endoplasmic reticulum ( ER) and the Golgi apparatus. Consistent with this finding, FRAP/mTOR is cofractionated with calnexin, an ER marker protein. Biochemical characterization suggests that FRAP/mTOR is a peripheral ER/Golgi protein with tight membrane association. Finally, we have identified domains of FRAP/mTOR which may mediate its association with the ER and the Golgi apparatus.