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Zen-ichiro Honda^1,2,*,, Takeshi Suzuki^1a and Hiroaki Honda³

¹ Department of Allergy and Rheumatology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
² Department of Health Service for Hospital Employees, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
³ Department of Developmental Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan

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.

These authors contributed equally to this work.

^aPresent address: Mitsui Memorial Hospital, Kanda Izumicho, Chiyoda-ku, Tokyo 101-0024, Japan.

^* honda-phy{at}h.u-tokyo.ac.jp