title: Critical role of the FERM domain in Pyk2 stimulated glioma cell migration.
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.
authors.affiliation: Mayo Clinic Arizona, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lipinski
authors.forename: Nhan L
authors.initials: NL
authors.lastname: Tran
authors.forename: Andrea
authors.initials: A
authors.lastname: Dooley
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Pang
authors.forename: Carole
authors.initials: C
authors.lastname: Rohl
authors.forename: Jean
authors.initials: J
authors.lastname: Kloss
authors.forename: Zhongbo
authors.initials: Z
authors.lastname: Yang
authors.forename: Wendy
authors.initials: W
authors.lastname: McDonough
authors.forename: David
authors.initials: D
authors.lastname: Craig
authors.forename: Michael E
authors.initials: ME
authors.lastname: Berens
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Loftus
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002522:Chlorocebus aethiops; D051418:Focal Adhesion Kinase 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D017434:Protein Structure, Tertiary
chemical_list: D051418:Focal Adhesion Kinase 2