The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif
The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif
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DOI：
10.1074/jbc.c200665200
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发表时间：
2003-05-02
影响因子：
4.8
通讯作者：
Yonezawa, K
中科院分区：
文献类型：
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作者：
Nojima, H;Tokunaga, C;Yonezawa, K
哺乳动物雷帕霉素靶蛋白（mTOR）通过调节p70s6激酶（p70S6k）和真核起始因子4e结合蛋白1 （4E-BP1）的磷酸化，控制多种细胞功能以响应氨基酸和生长因子。Raptor （mTOR的调控相关蛋白）是最近发现的mTOR结合伙伴，它也结合p70S6k和4E-BP1，对体内TOR信号传导至关重要。本研究表明，raptor通过各自的TOS（保守TOR信号）基元与p70S6k和4E-BP1结合，这是体内这些mTOR底物的氨基酸和mTOR依赖调控所必需的。TOS基元的点突变也消除了所有体外mtor催化的4E-BP1磷酸化，并消除了体外mtor催化的p70S6k磷酸化的raptor依赖成分。Raptor似乎是一种mTOR支架蛋白，其与mTOR底物的TOS基序列的结合是体内有效的mTOR催化磷酸化所必需的，也可能是赋予它们对雷帕霉素和氨基酸充足的敏感性所必需的。
The mammalian target of rapamycin (mTOR) controls multiple cellular functions in response to amino acids and growth factors, in part by regulating the phosphorylation of p70 S6 kinase (p70S6k) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Raptor (regulatory associated protein of mTOR) is a recently identified mTOR binding partner that also binds p70S6k and 4E-BP1 and is essential for TOR signaling in vivo. Herein we demonstrate that raptor binds to p70S6k and 4E-BP1 through their respective TOS (conserved TOR signaling) motifs to be required for amino acid- and mTOR-dependent regulation of these mTOR substrates in vivo. A point mutation of the TOS motif also eliminates all in vitro mTOR-catalyzed 4E-BP1 phosphorylation and abolishes the raptor-dependent component of mTOR-catalyzed p70S6k phosphorylation in vitro. Raptor appears to serve as an mTOR scaffold protein, the binding of which to the TOS motif of mTOR substrates is necessary for effective mTOR-catalyzed phosphorylation in vivo and perhaps for conferring their sensitivity to rapamycin and amino acid sufficiency.