The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase
The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase
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DOI：
10.1093/embo-reports/kvf197
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发表时间：
2002-10-01
期刊：
影响因子：
7.7
通讯作者：
Zheng, XFS
中科院分区：
文献类型：
--
作者：
Choi, JH;Bertram, PG;Zheng, XFS
CLIP-170/Restin属于保守的微管（MT）相关蛋白家族，对MT的组织和功能至关重要。CLIP-170是一种磷酸化蛋白，磷酸化被认为可以调节CLIP-170与MTs的结合。然而，对所涉及的激酶知之甚少。在这项研究中，我们发现fkbp12 -雷帕霉素相关蛋白（FRAP，也称为mTOR/RAFT）与CLIP-170相互作用。CLIP-170在体内多个位点被磷酸化，包括雷帕霉素敏感位点和非敏感位点，并且在体外被FRAP磷酸化雷帕霉素敏感位点。此外，雷帕霉素抑制了CLIP-170与mt结合的能力。我们的观察结果表明，CLIP-170的阳性和阴性控制涉及多个CLIP-170激酶，而FRAP是CLIP-170激酶正向调节CLIP-170的mt结合行为。
CLIP-170/Restin belongs to a family of conserved microtubule (MT)-associated proteins, which are important for MT organization and functions. CLIP-170 is a phosphoprotein and phosphorylation is thought to regulate the binding of CLIP-170 to MTs. However, little is known about the kinase(s) involved. In this study, we show that FKBP12-rapamycin-associated protein (FRAP, also called mTOR/RAFT) interacts with CLIP-170. CLIP-170 is phosphorylated in vivo at multiple sites, including rapamycin-sensitive and -insensitive sites, and is phosphorylated by FRAP in vitro at the rapamycin-sensitive sites. In addition, rapamycin inhibited the ability of CLIP-170 to bind to MTs. Our observations suggest that multiple CLIP-170 kinases are involved in positive and negative control of CLIP-170, and FRAP is a CLIP-170 kinase positively regulating the MT-binding behavior of CLIP-170.