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Activation of c‐Jun amino‐terminal kinase by GDNF induces G2/M cell cycle delay linked with actin reorganization
Author(s) -
Fukuda Toshifumi,
Asai Naoya,
Enomoto Atsushi,
Takahashi Masahide
Publication year - 2005
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2005.00866.x
Subject(s) - cyclin dependent kinase , biology , microbiology and biotechnology , cyclin dependent kinase 1 , cyclin a , cell cycle , cyclin dependent kinase 3 , cyclin b1 , wee1 , cyclin dependent kinase 2 , polo like kinase , restriction point , cyclin b , kinase , cyclin , protein kinase a , biochemistry , cell
It is well known that the cell cycle is controlled by several cyclin/cyclin‐dependent kinase (Cdk) complexes whose expression and phosphorylation states vary with orderly periodicity. During the cell cycle, activity of the cyclin/Cdk complexes can be regulated directly or indirectly by a number of molecules, including protein kinases and phosphatases, p53, and Cdk inhibitors. Here, we show that the addition of glial cell line‐derived neurotrophic factor (GDNF) induced G2/M cell cycle delay in human SK‐N‐MC neuroectodermal tumor cells that express RET tyrosine kinase, accompanying actin reorganization. Cell cycle delay at G2/M was characterized by accelerated and prolonged Cdc2 phosphorylation and stabilization of cyclin B1 and Wee1 kinase expression. Interestingly, we found that phosphorylation and/or expression of Cdc2, cyclinB1, and Wee1 was controlled by the Rac1/c‐Jun NH 2 ‐terminal kinase (JNK) pathway. Immunohistochemical analysis suggested that the G2/M cell cycle delay may be necessary to prevent the mitotic progression of SK‐N‐MC cells with perturbed actin cytoskeletons.