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. |