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

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
Zen-Ichiro HondaHiroaki Honda

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...Continue Reading

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Citations

May 22, 2010·Molecular and Cellular Biochemistry·Hirendra Nath BanerjeeMillon Blackshear
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Souvik DeySrinivasan Vijayaraghavan
Jan 11, 2020·Frontiers in Cell and Developmental Biology·Souvik DeySrinivasan Vijayaraghavan

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