Phosphorylation controls autoinhibition of cytoplasmic linker protein-170 Lee, Ho-Sup Komarova, Yulia A. Nadezhdina, Elena S. Anjum, Rana Peloquin, John G. Schober, Joseph M. Danciu, Oana van Haren, Jeffrey Galjart, Niels Gygi, Steven P. Akhmanova, Anna Borisy, Gary G. 2010-08-04T15:25:36Z 2010-08-04T15:25:36Z 2010-06-02
dc.description Author Posting. © American Society for Cell Biology, 2010. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 21 (2010): 2661-2673, doi:10.1091/mbc.E09-12-1036. en_US
dc.description.abstract Cytoplasmic linker protein (CLIP)-170 is a microtubule (MT) plus-end-tracking protein that regulates MT dynamics and links MT plus ends to different intracellular structures. We have shown previously that intramolecular association between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to MTs and the dynactin subunit p150Glued (J. Cell Biol. 2004: 166, 1003–1014). In this study, we demonstrate that conformational changes in CLIP-170 are regulated by phosphorylation that enhances the affinity between the N- and C-terminal domains. By using site-directed mutagenesis and phosphoproteomic analysis, we mapped the phosphorylation sites in the third serine-rich region of CLIP-170. A phosphorylation-deficient mutant of CLIP-170 displays an "open" conformation and a higher binding affinity for growing MT ends and p150Glued as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150Glued. We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition. en_US
dc.description.sponsorship This work was supported by National Institutes of Health grant GM-25062 (to G.G.B.); Netherlands Organization for Scientific Research grants (to A. A. and N. G.); a Cancer Genomics Centre grant (to J.v.H.); and Presidential Program of Russian Academy of Sciences and RFBP grant 05-04-4915 (to E.S.N.). en_US
dc.format.mimetype application/pdf
dc.identifier.citation Molecular Biology of the Cell 21 (2010): 2661-2673 en_US
dc.identifier.doi 10.1091/mbc.E09-12-1036
dc.language.iso en_US en_US
dc.publisher American Society for Cell Biology en_US
dc.title Phosphorylation controls autoinhibition of cytoplasmic linker protein-170 en_US
dc.type Article en_US
dspace.entity.type Publication
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