title: Identification of CENP-V as a novel microtubule-associating molecule that activates Src family kinases through SH3 domain interaction.
abstract: 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.
authors.affiliation: 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. honda-phy@h.u-tokyo.ac.jp
authors.forename: Zen-Ichiro
authors.initials: Z
authors.lastname: Honda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Honda
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D018386:Kinetochores; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination; D014945:Wound Healing; D018909:src Homology Domains / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C532477:CENPV protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases