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

Genes Cells. 2005 Jul;10(7):655-63. doi: 10.1111/j.1365-2443.2005.00866.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Nerve Growth Factors / metabolism*
  • Neuroectodermal Tumors / genetics
  • Neuroectodermal Tumors / metabolism
  • Nuclear Proteins / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured
  • rac1 GTP-Binding Protein / metabolism


  • 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