Table of Contents
Journal of Signal Transduction
Volume 2013, Article ID 956580, 12 pages
Research Article

A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration

1Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA
2Translational Genomics Research Institute, Phoenix, AZ 85004, USA

Received 17 June 2013; Revised 7 August 2013; Accepted 15 August 2013

Academic Editor: Matthias Gaestel

Copyright © 2013 Joseph C. Loftus et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Glioma cell migration correlates with Pyk2 activity, but the intrinsic mechanism that regulates the activity of Pyk2 is not fully understood. Previous studies have supported a role for the N-terminal FERM domain in the regulation of Pyk2 activity as mutations in the FERM domain inhibit Pyk2 phosphorylation. To search for novel protein-protein interactions mediated by the Pyk2 FERM domain, we utilized a yeast two-hybrid genetic selection to identify the mammalian Ste20 homolog MAP4K4 as a binding partner for the Pyk2 FERM domain. MAP4K4 coimmunoprecipitated with Pyk2 and was a substrate for Pyk2 but did not coimmunoprecipitate with the closely related focal adhesion kinase FAK. Knockdown of MAP4K4 expression inhibited glioma cell migration and effectively blocked Pyk2 stimulation of glioma cell. Increased expression of MAP4K4 stimulated glioma cell migration; however, this stimulation was blocked by knockdown of Pyk2 expression. These data support that the interaction of MAP4K4 and Pyk2 is integrated with glioma cell migration and suggest that inhibition of this interaction may represent a potential therapeutic strategy to limit glioblastoma tumor dispersion.