DOI: 10.1093/embo-reports/kvf197. The FKBP12‐rapamycin‐associated protein (FRAP) is a CLIP‐170 kinase

The FKBP12‐rapamycin‐associated protein (FRAP) is a CLIP‐170 kinase

10.1093/embo-reports/kvf197

Crossref journal-article

Springer Science and Business Media LLC

EMBO reports (297)

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.

Bibliography

Choi, J. H., Bertram, P. G., Drenan, R., Carvalho, J., Zhou, H. H., & Zheng, X. F. S. (2002). The FKBP12ârapamycinâassociated protein (FRAP) is a CLIPâ170 kinase. EMBO Reports, 3(10), 988â994. Portico.

Authors 6

Jae H Choi (first)
Paula G Bertram (additional)
Ryan Drenan (additional)
John Carvalho (additional)
Heather H Zhou (additional)
X F Steven Zheng (additional)

References 37 Referenced 81

10.1016/S0952-7915(98)80172-6
10.1016/S0092-8674(01)00288-4
10.1038/ng1095-115
10.1083/jcb.111.6.2573
10.1074/jbc.M004235200
10.1002/j.1460-2075.1992.tb05269.x
10.1038/369756a0
10.1038/377441a0
10.1126/science.277.5322.99
10.1016/S0092-8674(00)00091-X
10.1073/pnas.95.4.1432
10.1016/S0955-0674(99)80017-9
10.1016/S0960-9822(00)00599-6
10.1016/S0896-6273(00)80411-0
10.1182/blood.V80.11.2891.2891 / Blood / Expression of the novel intermediate filament‐associated protein restin in Hodgkin's disease and anaplastic large‐cell lymphoma by Delabie J. (1992)
10.3109/10428199309059567
10.1016/S0959-437X(99)80007-0
10.1146/annurev.cellbio.13.1.83
10.1101/gad.887201 / Genes Dev. / Regulation of translation initiation by FRAP/mTOR by Gingras A.‐C. (2001)
10.1242/jcs.113.12.2285
10.1016/S1074-5521(99)80070-2
10.1083/jcb.140.4.897
10.1016/S0960-9822(01)00286-X
10.1016/S0092-8674(00)80656-X
10.1016/0092-8674(92)90240-D
10.1073/pnas.121145898
10.1016/S0021-9258(19)47414-0
10.1074/jbc.R000034200
10.1038/sj.onc.1204059
10.1016/0092-8674(94)90570-3
10.1016/S0960-9822(00)00819-8
10.1074/jbc.274.36.25883
10.1016/S0092-8674(00)00117-3
10.1016/S0092-8674(01)00364-6
10.1006/bbrc.1997.7878
10.1038/35050669
10.1016/0092-8674(95)90058-6

Dates

Type	When
Created	22 years, 10 months ago (Oct. 7, 2002, 5:24 p.m.)
Deposited	1 year, 8 months ago (Dec. 18, 2023, 3:54 p.m.)
Indexed	2 months, 1 week ago (June 24, 2025, 8:28 p.m.)
Issued	22 years, 11 months ago (Oct. 1, 2002)
Published	22 years, 11 months ago (Oct. 1, 2002)
Published Online	22 years, 11 months ago (Oct. 1, 2002)
Published Print	22 years, 11 months ago (Oct. 1, 2002)

Funders 0

None

BibTeX

@article{Choi_2002, title={The FKBP12‐rapamycin‐associated protein (FRAP) is a CLIP‐170 kinase}, volume={3}, ISSN={1469-3178}, url={http://dx.doi.org/10.1093/embo-reports/kvf197}, DOI={10.1093/embo-reports/kvf197}, number={10}, journal={EMBO reports}, publisher={Springer Science and Business Media LLC}, author={Choi, Jae H and Bertram, Paula G and Drenan, Ryan and Carvalho, John and Zhou, Heather H and Zheng, X F Steven}, year={2002}, month=oct, pages={988–994} }

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  "abstract": "<jats:p>CLIP\u2010170/Restin belongs to a family of conserved microtubule (MT)\u2010associated proteins, which are important for MT organization and functions. CLIP\u2010170 is a phosphoprotein and phosphorylation is thought to regulate the binding of CLIP\u2010170 to MTs. However, little is known about the kinase(s) involved. In this study, we show that FKBP12\u2010rapamycin\u2010associated protein (FRAP, also called mTOR/RAFT) interacts with CLIP\u2010170. CLIP\u2010170 is phosphorylated <jats:italic>in vivo</jats:italic> at multiple sites, including rapamycin\u2010sensitive and \u2010insensitive sites, and is phosphorylated by FRAP <jats:italic>in vitro</jats:italic> at the rapamycin\u2010sensitive sites. In addition, rapamycin inhibited the ability of CLIP\u2010170 to bind to MTs. Our observations suggest that multiple CLIP\u2010170 kinases are involved in positive and negative control of CLIP\u2010170, and FRAP is a CLIP\u2010170 kinase positively regulating the MT\u2010binding behavior of CLIP\u2010170.</jats:p>",
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