Ho-Sup Lee

Publications (1)5.98 Total impact

• Article: Phosphorylation controls autoinhibition of cytoplasmic linker protein-170.

  Ho-Sup Lee, Yulia A Komarova, Elena S Nadezhdina, Rana Anjum, John G Peloquin, Joseph M Schober, Oana Danciu, Jeffrey van Haren, Niels Galjart, Steven P Gygi, Anna Akhmanova, Gary G Borisy
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  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 p150(Glued) (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 p150(Glued) as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150(Glued). We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition.
  Molecular biology of the cell 08/2010; 21(15):2661-73. · 5.98 Impact Factor