Activation of c-Jun amino-terminal kinase by GDNF induces G2/M cell cycle delay linked with actin reorganization.

Abstract

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 NH2-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.

• Authors: Toshifumi Fukuda, Naoya Asai, Atsushi Enomoto, Masahide Takahashi
• Journal: Genes to cells : devoted to molecular & cellular mechanisms (Genes Cells) Vol. 10 Issue 7 Pg. 655-63 (Jul 2005) ISSN: 1356-9597 [Print] England
• PMID: 15966897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• CCNB1 protein, human
• Cell Cycle Proteins
• Cyclin B
• Cyclin B1
• GDNF protein, human
• Glial Cell Line-Derived Neurotrophic Factor
• Mitogens
• Nerve Growth Factors
• Nuclear Proteins
• Oncogene Proteins
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-ret
• RET protein, human
• Receptor Protein-Tyrosine Kinases
• WEE1 protein, human
• CDC2 Protein Kinase
• JNK Mitogen-Activated Protein Kinases
• rac1 GTP-Binding Protein

Topics

• Actins (metabolism)
• CDC2 Protein Kinase (metabolism)
• Cell Cycle Proteins (metabolism)
• Cell Division
• Cell Proliferation
• Cyclin B (metabolism)
• Cyclin B1
• Enzyme Activation
• Enzyme Stability
• G2 Phase
• Glial Cell Line-Derived Neurotrophic Factor
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Mitogens (metabolism)
• Nerve Growth Factors (genetics, metabolism)
• Neuroectodermal Tumors (genetics, metabolism)
• Nuclear Proteins (metabolism)
• Oncogene Proteins (genetics, metabolism)
• Phosphorylation
• Protein-Tyrosine Kinases (metabolism)
• Proto-Oncogene Proteins c-ret
• Receptor Protein-Tyrosine Kinases (genetics, metabolism)
• Signal Transduction
• Tumor Cells, Cultured
• rac1 GTP-Binding Protein (metabolism)