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Published online 23 September 2002. doi:10.1083/jcb.200207008
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© The Rockefeller University Press, 0021-9525/2002/9/1287 $5.00
The Journal of Cell Biology, Volume 158, Number 7, September 30, 2002 1287-1297

Article

 p21-activated kinase 4 interacts with integrin {alpha}vß5 and regulates {alpha}vß5-mediated cell migration

Hongquan Zhang1, Zhilun Li1, Eva-Karin Viklund1 and Staffan Strömblad1,2

1 Karolinska Institutet, Department of Microbiology, Pathology, and Immunology, SE-141 86 Huddinge, Sweden
2 Södertörns Högskola, SE-141 89 Huddinge, Sweden

Address correspondence to Staffan Strömblad, Karolinska Institutet, Department of Microbiology, Pathology, and Immunology, Huddinge University Hospital F46, SE-141 86 Huddinge, Sweden. Tel.: 46-8-585-81032. Fax: 46-8-585-81020. E-mail: staffan.stromblad{at}impi.ki.se

p21-activated kinase 1 (PAK1) can affect cell migration (Price et al., 1998; del Pozo et al., 2000) and modulate myosin light chain kinase and LIM kinase, which are components of the cellular motility machinery (Edwards, D.C., L.C. Sanders, G.M. Bokoch, and G.N. Gill. 1999. Nature Cell Biol. 1:253–259; Sanders, L.C., F. Matsumura, G.M. Bokoch, and P. de Lanerolle. 1999. Science. 283:2083–2085). We here present a novel cell motility pathway by demonstrating that PAK4 directly interacts with an integrin intracellular domain and regulates carcinoma cell motility in an integrin-specific manner. Yeast two-hybrid screening identified PAK4 binding to the cytoplasmic domain of the integrin ß5 subunit, an association that was also found in mammalian cells between endogenous PAK4 and integrin {alpha}vß5. Furthermore, we mapped the PAK4 binding to the membrane-proximal region of integrin ß5, and identified an integrin-binding domain at aa 505–530 in the COOH terminus of PAK4. Importantly, engagement of integrin {alpha}vß5 by cell attachment to vitronectin led to a redistribution of PAK4 from the cytosol to dynamic lamellipodial structures where PAK4 colocalized with integrin {alpha}vß5. Functionally, PAK4 induced integrin {alpha}vß5–mediated, but not ß1-mediated, human breast carcinoma cell migration, while no changes in integrin cell surface expression levels were observed. In conclusion, our results demonstrate that PAK4 interacts with integrin {alpha}vß5 and selectively promotes integrin {alpha}vß5–mediated cell migration.

Key Words: cell motility; cell signaling; integrin; lamellipodia; p21-activated kinase


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