Cdc2-mediated phosphorylation of CLIP-170 is essential for its inhibition of centrosome reduplication.
CLIP-170, the founding member of microtubule "plus ends tracking" proteins, is involved in many critical microtubule-related functions, including recruitment of dynactin to the microtubule plus ends and formation of kinetochore-microtubule attachments during metaphase. Although it has been reported that CLIP-170 is a phosphoprotein, neither have individual phosphorylation sites been identified ... nor have the associated kinases been extensively studied. Herein, we identify Cdc2 as a kinase that phosphorylates CLIP-170. We show that Cdc2 interacts with CLIP-170 mediating its phosphorylation on Thr(287) in vivo. Significantly, expression of CLIP-170 with a threonine 287 to alanine substitution (T287A) results in its mislocalization, accumulation of Plk1 and cyclin B, and block of the G2/M transition. Finally, we found that depletion of CLIP-170 leads to centrosome reduplication and that Cdc2 phosphorylation of CLIP-170 is required for the process. These results demonstrate that Cdc2-mediated phosphorylation of CLIP-170 is essential for the normal function of this protein during cell cycle progression.
Mesh Terms:
Animals, CDC2 Protein Kinase, Cell Cycle, Cell Line, Cell Line, Tumor, Centrosome, Cyclin B, Cyclin-Dependent Kinases, Humans, Microtubule-Associated Proteins, Microtubules, Neoplasm Proteins, Peptides, Phenotype, Phosphorylation, Rats, Recombinant Proteins, Tubulin
Animals, CDC2 Protein Kinase, Cell Cycle, Cell Line, Cell Line, Tumor, Centrosome, Cyclin B, Cyclin-Dependent Kinases, Humans, Microtubule-Associated Proteins, Microtubules, Neoplasm Proteins, Peptides, Phenotype, Phosphorylation, Rats, Recombinant Proteins, Tubulin
J Biol Chem
Date: Oct. 16, 2009
PubMed ID: 19687009
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