The tyrosine kinase pyk2 promotes migration and invasion of glioma cells.
Glioblastoma multiforme is extraordinarily aggressive due to the propensity of cells to migrate away from the tumor core into the surrounding normal brain. In this report, we investigated the role of proline-rich tyrosine kinase 2 (Pyk2) and FAK with regard to influencing glioma cell phenotypes. Expression of Pyk2 stimulated glioma cell migration, whereas expression of FAK inhibited glioma cell migration and stimulated cell cycle progression. Pyk2 autophosphorylation was necessary, but not sufficient, to stimulate cellular migration. The N-terminal domain of Pyk2 is required for stimulation of migration as an N-terminally deleted variant of Pyk2 failed to stimulate migration, whereas expression of an autonomous Pyk2 N-terminal domain inhibited cell migration. Substitution of the C-terminal domain of Pyk2 with the corresponding domain of FAK stimulated cell migration as effectively as wild-type Pyk2; however, substitution of the N-terminal domain of Pyk2 with that of FAK inhibited cell migration, substantiating that the N-terminal domain of Pyk2 was required to stimulate migration. Silencing of Pyk2 expression by RNA interference significantly inhibited glioma migration. Cell migration was restored on re-expression of Pyk2, but expression of FAK in Pyk2 knockdown cells failed to restore migration. We conclude that Pyk2 plays a central role in the migratory behavior of glioblastomas.
Lipinski
Christopher A
CA
Mayo Clinic Scottsdale, Scottsdale, AZ 85259, USA.
Tran
Nhan L
NL
Menashi
Emmanuel
E
Rohl
Carole
C
Kloss
Jean
J
Bay
R Curtis
RC
Berens
Michael E
ME
Loftus
Joseph C
JC
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000737:chemistry; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017353:Gene Deletion; D020868:Gene Silencing; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D013997:Time Factors
D000939:Epitopes; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496052:Ptk2 protein, rat; C496054:Ptk2b protein, rat