Focal adhesion kinase is required for endothelin-induced cell cycle progression of cultured astrocytes.
When the brain is damaged, astrocytes often cause hyperplasia resulting in glial scar formation at the injured sites. Endothelins (ETs) have been shown to be involved in the pathophysiologic responses of astrocytes, including proliferation. In this study, we examined the mechanisms underlying the ET-induced astrocytic G1/S-phase cell cycle transition by focusing on focal adhesion kinase (FAK). A transient transfection with wild-type FAK was followed by an increase in bromodeoxyuridine (BrdU) incorporation into cultured rat astrocytes. The increases in BrdU incorporation induced by 100 nM ET-1 were not found in astrocytes transfected with dominant-negative FAK mutants (FRNK and dC14-FAK). The increases in BrdU incorporation induced by 10 nM phorbol 12-myristate 13-acetate (PMA) were not affected by the FAK mutants. Wild-type FAK did not induce stress fiber formation in cultured astrocytes. The dominant negative FAK mutant dC14-FAK did not prevent ET-induced astrocytic stress fiber formation. These results suggest that FAK mediated the astrocytic G1/S cell cycle transition induced by ET-1 downstream of the cytoskeletal actin reorganization.
Koyama
Yutaka
Y
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Yoshioka
Yasuhiro
Y
Matsuda
Toshio
T
Baba
Akemichi
A
D000199:Actins / Q000378:metabolism; D000661:Amphetamine; D000662:Amphetamines; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005822:Genetic Vectors / Q000378:metabolism; D009154:Mutation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D014162:Transfection / Q000379:methods
D000199:Actins; D000662:Amphetamines; D016232:Endothelins; D019000:Phosphotyrosine; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D000661:Amphetamine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D001973:Bromodeoxyuridine; D013755:Tetradecanoylphorbol Acetate; C100230:4-methoxyamphetamine