Critical role of the FERM domain in Pyk2 stimulated glioma cell migration

Christopher A Lipinski, Nhan L. Tran, Andrea Dooley, Yuan Ping Pang, Carole Rohl, Jean Kloss, Zhongbo Yang, Wendy McDonough, David Craig, Michael E. Berens, Joseph C. Loftus

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The strong tendency of malignant glioma cells to invade locally into surrounding normal brain precludes effective surgical resection, reduces the efficacy of radiotherapy, and is associated with increased resistance to chemotherapy regimens. We report that the N-terminal FERM domain of Pyk2 regulates its promigratory function. A 3-dimensional model of the Pyk2 FERM domain was generated and mutagenesis studies identified residues essential for Pyk2 promigratory function. Model-based targeted mutations within the FERM domain decreased Pyk2 phosphorylation and reduced the capacity of Pyk2 to stimulate glioma cell migration but did not significantly alter the intracellular distribution of Pyk2. Expression of autonomous Pyk2 FERM domain fragments containing analogous mutations exhibited reduced capacity to inhibit glioma cell migration and Pyk2 phosphorylation relative to expression of an autonomous wild type FERM domain fragment. These results indicate that the FERM domain plays an important role in regulating the functional competency of Pyk2 as a promigratory factor in glioma.

Original languageEnglish (US)
Pages (from-to)939-947
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume349
Issue number3
DOIs
StatePublished - Oct 27 2006

Keywords

  • Focal adhesion kinase
  • Glioma
  • Invasion
  • Migration
  • Pyk2
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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