This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Paliouras, G. N.
Right arrow Articles by Park, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Paliouras, G. N.
Right arrow Articles by Park, M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2009, p. 3018-3032, Vol. 29, No. 11
0270-7306/09/$08.00+0     doi:10.1128/MCB.01286-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Pak4, a Novel Gab1 Binding Partner, Modulates Cell Migration and Invasion by the Met Receptor{triangledown} ,{dagger}

Grigorios N. Paliouras,1,2,¶ Monica A. Naujokas,1,¶ and Morag Park1,2,3,4,¶*

Molecular Oncology Group, McGill University Health Centre, Royal Victoria Hospital, 687 Avenue des Pins Ouest, Montreal, Quebec H3A 1A1, Canada,1 Departments of Experimental Medicine,2 Biochemistry,3 Oncology, McGill University, Montreal, Quebec, Canada4

Received 13 August 2008/ Returned for modification 24 October 2008/ Accepted 9 March 2009

Hepatocyte growth factor (HGF), the ligand for the Met receptor tyrosine kinase, induces epithelial cell dispersal, invasion, and morphogenesis, events that require remodeling of the actin cytoskeleton. The scaffold protein Gab1 is essential for these biological responses downstream from Met. We have identified p21-activated kinase 4 (Pak4) as a novel Gab1-interacting protein. We show that in response to HGF, Gab1 and Pak4 associate and colocalize at the cell periphery within lamellipodia. The association between Pak4 and Gab1 is dependent on Gab1 phosphorylation but independent of Pak4 kinase activity. The interaction is mediated through a region in Gab1, which displays no homology to known Gab1 interaction motifs and through the guanine exchange factor-interacting domain of Pak4. In response to HGF, Gab1 and Pak4 synergize to enhance epithelial cell dispersal, migration, and invasion, whereas knockdown of Pak4 attenuates these responses. A Gab1 mutant unable to recruit Pak4 fails to promote epithelial cell dispersal and an invasive morphogenic program in response to HGF, demonstrating a physiological requirement for Gab1-Pak4 association. These data demonstrate a novel association between Gab1 and Pak4 and identify Pak4 as a key integrator of cell migration and invasive growth downstream from the Met receptor.

* Corresponding author. Mailing address: Goodman Cancer Centre, 1160 Avenue des Pins Ouest, Room 511, Montreal, Quebec H3G 1Y6, Canada. Phone: (514) 398-5749. Fax: (514) 398-6769. E-mail: morag.park{at}mcgill.ca

{triangledown} Published ahead of print on 16 March 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: Goodman Cancer Centre, 1160 Avenue des Pins Ouest, Room 511, Montreal, Quebec H3G 1Y6, Canada.

Molecular and Cellular Biology, June 2009, p. 3018-3032, Vol. 29, No. 11
0270-7306/09/$08.00+0     doi:10.1128/MCB.01286-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»