Cas utilizes Nck2 to activate Cdc42 and regulate cell polarization during cell migration in response to wound healing.
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.
Funasaka
Kohei
K
Department of Gastroenterology, Nagoya University Graduate School of Medicine, Japan.
Ito
Satoko
S
Hasegawa
Hitoki
H
Goldberg
Gary S
GS
Hirooka
Yoshiki
Y
Goto
Hidemi
H
Hamaguchi
Michinari
M
Senga
Takeshi
T
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*
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