Science：蒋玉白小川—细胞生长调控研究
来自匹兹堡大学医学院药理学系、神经学系、南方医科大学基础医学院细胞生物学系的研究人员发现了重要的细胞生长关键调控因子：mTOR作用途径中的新成员，而这一新成员的抑制作用会受到另一因子的抑制，这对于研究细胞生长调控及增殖、探索靶向mTOR的治疗肿瘤的药物意义重大。这一研究成果公布在《科学》杂志上。
文章的通讯作者是来自匹兹堡大学医学院的蒋玉（Yu Jiang，音译）博士，第一作者为同属于匹兹堡大学和南方医科大学的白小川（Xiaochun Bai，音译）博士。
哺乳类动物雷帕霉素靶蛋白(The mammalian target of rapamycin，mTOR）是一种重要的细胞生长调控因子，在蛋白激酶调节细胞存活、增殖和血管生成的信号转导途径中起到重要作用。之前mTOR一直被作为免疫抑制药物雷帕霉素的靶标进行研究。
随着研究的深入，科学家们发现mTOR是由Rheb——一种Ras-like小鸟嘌呤核甘三磷酸酶（small guanosine triphosphatase，GTPase），能对生长因子刺激和营养获得作出应答。在这篇文章中，研究人员发现Rheb调节mTOR的机理：即通过一种FK506绑定蛋白（FK506-binding protein，FKBP）家族的成员——FKBP38进行调控。
研究人员通过实验发现FKBP38绑定在mTOR上，以一种类似于FKBP12-rapamycin复合物作用机理的方式抑制mTOR的活性。而且Rheb也可以直接与FKBP38相互作用，阻止它与mTOR以一种依赖于GTP的方式相互作用。
这些研究结果表明FKBP38是mTOR的一个内源性的抑制子，而这种抑制活性会由于生长因子的刺激和获得营养被Rheb拮抗。
原始出处:
Science 9 November 2007:
Vol. 318. no. 5852, pp. 977 - 980
DOI: 10.1126/science.1147379
Rheb Activates mTOR by Antagonizing Its Endogenous Inhibitor, FKBP38
Xiaochun Bai,1,3 Dongzhu Ma,1 Anling Liu,1 Xiaoyun Shen,1 Qiming J. Wang,1 Yongjian Liu,2 Yu Jiang1*
The mammalian target of rapamycin, mTOR, is a central regulator of cell growth. Its activity is regulated by Rheb, a Ras-like small guanosine triphosphatase (GTPase), in response to growth factor stimulation and nutrient availability. We show that Rheb regulates mTOR through FKBP38, a member of the FK506-binding protein (FKBP) family that is structurally related to FKBP12. FKBP38 binds to mTOR and inhibits its activity in a manner similar to that of the FKBP12-rapamycin complex. Rheb interacts directly with FKBP38 and prevents its association with mTOR in a guanosine 5'-triphosphate (GTP)–dependent manner. Our findings suggest that FKBP38 is an endogenous inhibitor of mTOR, whose inhibitory activity is antagonized by Rheb in response to growth factor stimulation and nutrient availability.
1 Department of Pharmacology, University of Pittsburgh School of Medicine, E1357 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
2 Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
3 Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
* To whom correspondence should be addressed. E-mail: jiang@server.pharm.pitt.edu
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