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| Subject Categories: Cell & Tissue Architecture |
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| The EMBO Journal
(2006) 25, 1848–1859, doi:10.1038/sj.emboj.7601092 Published online 20 April 2006 |
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| GIT2 represses Crk- and Rac1-regulated cell spreading and Cdc42-mediated focal adhesion turnover |
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| Scott R Frank, Molly R Adelstein and Steen H Hansen |
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Boston Biomedical Research Institute, Watertown, MA, USA To whom correspondence should be addressed Steen H Hansen, GI Cell Biology Laboratory, Harvard Digestive Diseases Center, Enders 730.2, The Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. Tel.: +1 617 919 4544; Fax: +1 617 730 0498; E-mail: steen.hansen@childrens.harvard.edu Received 25 October 2005; Accepted 21 March 2006; Published online 20 April 2006. |
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| Abstract |
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G protein-coupled receptor kinase interactors (GITs) regulate focal adhesion (FA) turnover, cell spreading, and motility through direct interaction with paxillin and the Rac-exchange factor Pak-interacting exchange factor  (PIX). However, it is not clear whether GITs function to activate or repress motility or if the predominant GIT forms, GIT1 and GIT2, serve distinct or redundant roles. Here we demonstrate an obligatory role for endogenous GIT2 in repression of lamellipodial extension and FA turnover by Rac1- and Cdc42-dependent signaling pathways, respectively. Moreover, we show that the SH2–SH3 adaptor protein Crk is an essential target of GIT2 inhibition. Unexpectedly, we find that PIX is dispensable for the effects elicited by knockdown of GIT2. Finally, we show that loss of GIT2 is sufficient to induce migration of the nontransformed epithelial cell line MCF10A. These results suggest that inactivation of GIT2 function is a required step for induction of cell motility and that GIT2 may be a target of oncogenic signaling pathways that regulate cell migration. |
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| Keywords: Cdc42, Crk, GIT, PIX, Rac |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSCell polarization mechanisms during directed cell migration Nature Cell Biology News and Views (01 Apr 2005) Casting light on focal adhesions Nature Genetics News and Views (01 Aug 1998) RESEARCHA GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins Nature Immunology Article (01 Jun 2001) Nature Cell Biology Article (01 Apr 2005) |
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