Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway

Oncogene. 2006 Jul 13;25(30):4172-82. doi: 10.1038/sj.onc.1209449. Epub 2006 Feb 27.

Abstract

The subfamily of WNK (with no K= lysine) protein kinases has four human members and germline mutations in the WNK1 and WNK4 genes were recently found to cause pseudohypoaldosteronism type II, a familial hypertension disease. Here, we describe cloning and functional analysis of a further WNK member, human WNK3. Endogenous WNK3 protein is an active protein kinase when immunoprecipitated from cells and its overexpression increases the survival of HeLa cells by delaying the onset of apoptosis. Suppression of endogenous WNK3 protein by RNA interference accelerates the apoptotic response and promotes the activation of caspase-3. The mechanism of WNK3 action involves interaction with procaspase-3 and heat-shock protein 70. These results demonstrate a role for WNK3 in promoting cell survival and suggest a mechanism at the level of procaspase-3 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Caspase 3
  • Caspases / metabolism
  • Caspases / physiology*
  • Cell Line
  • Cell Survival / physiology
  • Enzyme Activation / physiology
  • Enzyme Precursors / metabolism
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / isolation & purification
  • Protein-Serine-Threonine Kinases / physiology*
  • Signal Transduction / physiology*

Substances

  • Enzyme Precursors
  • Protein-Serine-Threonine Kinases
  • WNK3 protein, human
  • CASP3 protein, human
  • Caspase 3
  • Caspases

Associated data

  • GENBANK/AJ409088