Human TAO kinase 1 induces apoptosis in SH-SY5Y cells

Cell Biol Int. 2008 Jan;32(1):151-6. doi: 10.1016/j.cellbi.2007.08.006. Epub 2007 Aug 30.

Abstract

The human TAO kinase 1 (hTAOK1) is a member of the Ste20 group of kinases with the kinase domain located at the N-terminus. The rat homologue, originally named TAO1, has been demonstrated to be highly expressed in brain. In this study, the human TAO kinase 1 was transfected into human neuroblastoma SH-SY5Y cells and its biological effects on the cell morphology were observed by co-expressing the enhanced green fluorescent protein (EGFP). It was found that after 16 h of transfection the cells had shrunk, and finally became rounded when transfected with wild-type or mutant K57A genes encoding either the kinase domain (residues 1-376) or the full-length molecule (residues 1-1001). Thirty-four hours after transfection, cells floated and apoptotic bodies were observed after nuclear staining with DAPI. On the other hand, the cells that were transfected with the gene encoding the C-terminal regulatory region (residues 377-1001) of hTAOK1, appeared to remain unchanged. In order to know the signaling events involved in the above biological phenomena, caspase-3-like activities of the transfected cells were measured in the absence or presence of JNK inhibitor SP600125, in which caspase-3 and JNK (C-jun-N-terminal kinase) are both known to be critical components of the neuronal apoptosis. The results showed that the apoptotic cells exhibited elevated caspase-3-like activity, which could be reduced by SP600125 to some extent. It is concluded that human TAO kinase 1 induces apoptosis in SH-SY5Y cells and the kinase domain is essential, but its catalytic activity seems to be dispensable in this case.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Kinase Kinases / metabolism*
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases
  • Transfection

Substances

  • Anthracenes
  • pyrazolanthrone
  • Protein-Serine-Threonine Kinases
  • TAO1 protein kinase
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • Caspase 3