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Publication : Identification of CENP-V as a novel microtubule-associating molecule that activates Src family kinases through SH3 domain interaction.

First Author  Honda Z Year  2009
Journal  Genes Cells Volume  14
Issue  12 Pages  1383-94
PubMed ID  19930468 Mgi Jnum  J:158482
Mgi Id  MGI:4438847 Doi  10.1111/j.1365-2443.2009.01355.x
Citation  Honda Z, et al. (2009) Identification of CENP-V as a novel microtubule-associating molecule that activates Src family kinases through SH3 domain interaction. Genes Cells 14(12):1383-94
abstractText  The activation mechanisms of Src family kinases (SFKs) involve the dissociation of the intramolecular interaction between the Src homology (SH) 3 and kinase domain. This process is mediated by the intermolecular attack of outer ligands to the SH3 domain. By using a yeast two-hybrid screen, we isolated a relevant ligand involved in the activation mechanisms of SFKs. This molecule was found to be identical to a recently recognized kinetochore protein--designated as centromere protein (CENP)-V--which is required for the progression of mitosis. We show here that human CENP-V plays further roles in cell dynamics; the proline-rich region of human CENP-V associates with the SH3 domains of SFKs and potently activates SFKs, whereas another domain of CENP-V that possesses a highly conserved cysteine array confers the ability to associate with stabilized microtubules (MTs). Human CENP-V distributes to the cell protrusion and to the leading edge of migrating cells in response to external stimuli, and depletion of CENP-V by RNA interference significantly attenuates closure of a scratch wound. These findings indicate that human CENP-V is involved in directional cell motility as well as in the progression of mitosis, as a scaffolding molecule that links MTs and SFKs.
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