title: Dock4 forms a complex with SH3YL1 and regulates cancer cell migration.
abstract: Dock4 is a member of the Dock180 family of proteins that mediates cancer cell migration through activation of Rac. However, the regulatory mechanism of Dock4 remains unclear. In this study, we show that the C-terminal proline-rich region of Dock4 is essential for the Dock4 mediated promotion of cell migration in MDA-MB-231 breast cancer cells. We found that a phosphoinositide-binding protein SH3YL1 interacted with the C-terminal proline-rich region of Dock4. Interaction of SH3YL1 with Dock4 promoted Dock4-mediated Rac1 activation and cell migration. Mutations in the phosphoinositide-binding domain disrupted the ability of SH3YL1 to promote Dock4-mediated cell migration. In addition, depletion of SH3YL1 in MDA-MB-231 cells suppressed cell migration. Taken together, these results provide evidence for a novel and functionally important interaction between Dock4 and SH3YL1 to promote cancer cell migration by regulating Rac1 activity.
authors: Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Masakazu
authors: M
authors: Kobayashi
authors: Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Kohei
authors: K
authors: Harada
authors: Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Manabu
authors: M
authors: Negishi
authors: Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: hirokato@pharm.kyoto-u.ac.jp.
authors: Hironori
authors: H
authors: Katoh
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C473475:Dock4 protein, mouse; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; C560582:SH3YL1 protein, human; D020830:rac1 GTP-Binding Protein
keywords: Cell migration; Dock4; GEF; Rac1; Rho family