TAILIEUCHUNG - Báo cáo khoa học: 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 dur-ing wound healing. After phosphorylation on tyrosine residues, Cas recruits the adaptor proteins Crk and Nck to execute integrin-mediated signals. | Cas utilizes Nck2 to activate Cdc42 and regulate cell polarization during cell migration in response to wound healing Kohei Funasaka1 Satoko Ito2 Hitoki Hasegawa2 Gary Yoshiki Hirooka1 Hidemi Goto1 Michinari Hamaguchi2 and Takeshi Senga2 1 Department of Gastroenterology Nagoya University Graduate Schoolof Medicine Japan 2 Division of Cancer Biology Nagoya University Graduate Schoolof Medicine Japan 3 Molecular Biology Department University of Medicine and Dentistry of New Jersey Stratford NJ USA Keywords Cas Cdc42 Crk Nck polarity Correspondence T. Senga Division of Cancer Biology Nagoya University Graduate Schoolof Medicine 65 Tsurumai-cho Showa-ku Nagoya 466-8550 Japan Fax 81 52 744 2464 Tel 81 52 744 2463 E-mail tsenga@ Received 14 April 2010 revised 1 June 2010 accepted 28 June 2010 doi 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. Structured digital abstract MINT-7909509 Cas uniprotkb Q61140 and Nck2 uniprotkb Q8BQ28 colocalize MI 0403 by fluorescence microscopy MI 0416 Introduction The establishment of cell polarity is essential for a variety of cellular functions such as cell division differentiation and migration however the molecular mechanisms underlying .

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