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Focal adhesion kinase is required for endothelin‐induced cell cycle progression of cultured astrocytes
Author(s) -
Koyama Yutaka,
Yoshioka Yasuhiro,
Matsuda Toshio,
Baba Akemichi
Publication year - 2003
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10240
Subject(s) - focal adhesion , biology , microbiology and biotechnology , ptk2 , transfection , paxillin , cytoskeleton , cell cycle , astrocyte , stress fiber , bromodeoxyuridine , signal transduction , protein kinase c , cell growth , cell culture , cell , endocrinology , biochemistry , central nervous system , mitogen activated protein kinase kinase , genetics
Abstract 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. © 2003 Wiley‐Liss, Inc.