title: The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase.
abstract: 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.
authors.affiliation: Myriad Proteonomics, Inc., Salt Lake City, UT 84116, USA.
authors.forename: Jae H
authors.initials: JH
authors.lastname: Choi
authors.forename: Paula G
authors.initials: PG
authors.lastname: Bertram
authors.forename: Ryan
authors.initials: R
authors.lastname: Drenan
authors.forename: John
authors.initials: J
authors.lastname: Carvalho
authors.forename: Heather H
authors.initials: HH
authors.lastname: Zhou
authors.forename: X F Steven
authors.initials: XF
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D002417:Cattle; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D020104:Immunophilins / Q000737:chemistry* / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D009363:Neoplasm Proteins; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor); D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C076744:cytoplasmic linker protein 170; D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020104:Immunophilins; D020123:Sirolimus