title: Cas utilizes Nck2 to activate Cdc42 and regulate cell polarization during cell migration in response to wound healing.
abstract: Integrin-mediated activation of Cdc42 is essential for cell polarization, whereas the integrin adaptor protein Cas is required for cell migration during wound healing. After phosphorylation on tyrosine residues, Cas recruits the adaptor proteins Crk and Nck to execute integrin-mediated signals. However, the mechanisms leading to Cdc42 activation and its relationship with Cas, Crk and Nck have not been elucidated clearly. In the present study, we demonstrate that Cas utilizes Nck2 to activate Cdc42 and induce cell polarization in response to wounding. By contrast, Cas recruits CrkII to activate Rac1 and promote the extension of cell protrusions needed for cell motility. These results indicate that Cas utilizes Nck2 and CrkII in a coordinated set of distinct pathways leading to cell migration.
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Funasaka
authors.forename: Satoko
authors.initials: S
authors.lastname: Ito
authors.forename: Hitoki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Gary S
authors.initials: GS
authors.lastname: Goldberg
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000378:metabolism*; D050737:Proto-Oncogene Proteins c-crk / Q000378:metabolism; D014945:Wound Healing; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; C117758:Nck2 protein, mouse; D015513:Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D020764:cdc42 GTP-Binding Protein