Article
- The EMBO Journal (2004) 23, 2777 - 2788
- doi:10.1038/sj.emboj.7600291
Published online: 1 July 2004
Subject Category:
The integrin-binding protein Nischarin regulates cell migration by inhibiting PAK
Suresh K Alaharia, Peter J Reddiga and Rudy L Juliano
- Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC USA
Correspondence to:
Rudy L Juliano, Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. Tel.: +1 919 966 4583; Fax: +1 919 966 5640; E-mail: arjay@med.unc.edu
aThese authors contributed equally to this work
Received 29 September 2003; Accepted 26 May 2004
Abstract
Nischarin, a novel intracellular protein, was originally identified as a binding partner for the 
5
1 integrin. Here we show that Nischarin also interacts with members of the PAK family of kinases. The amino terminus of Nischarin preferentially binds to the carboxy-terminal domain of PAK1 when the kinase is in its activated conformation. Nischarin binding to PAK1 is enhanced by active Rac, with the three proteins forming a complex, while expression of the 51 integrin also increases the Nischarin/PAK1 association. Interaction with Nischarin strongly inhibits the ability of PAK1 to phosphorylate substrates. This effect on PAK kinase activity closely parallels Nischarin's ability to inhibit cell migration. Conversely, reduction of endogenous levels of Nischarin by RNA interference promotes cell migration. In addition, PAK1 and Nischarin colocalize in membrane ruffles, structures known to be involved in cell motility. Thus, Nischarin may regulate cell migration by forming inhibitory complexes with PAK family kinases.
Keywords:
- cell migration,
- integrin,
- Nischarin,
- PAK
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