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Updated: Jul 27, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway
F Veríssimo1, E Silva, J D Morris
1Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa, Portugal.
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.
Insights
The WNK3 protein kinase promotes cell survival by delaying apoptosis. WNK3 interacts with procaspase-3, inhibiting its activation and preventing programmed cell death.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The WNK (with no K= lysine) protein kinase subfamily has four human members.
- Germline mutations in WNK1 and WNK4 genes are linked to pseudohypoaldosteronism type II, a familial hypertension disease.
Purpose of the Study:
- To clone and functionally analyze the human WNK3 protein kinase.
- To investigate the role of WNK3 in cell survival and apoptosis.
Main Methods:
- Cloning and overexpression of human WNK3.
- Immunoprecipitation and kinase assays of endogenous WNK3.
- RNA interference to suppress WNK3 expression.
- Analysis of apoptosis and caspase-3 activation.
- Investigation of protein interactions with procaspase-3 and HSP70.
Main Results:
- Endogenous WNK3 is an active protein kinase.
- WNK3 overexpression enhances HeLa cell survival by delaying apoptosis.
- WNK3 suppression accelerates apoptosis and promotes caspase-3 activation.
- WNK3 interacts with procaspase-3 and heat-shock protein 70.
Conclusions:
- WNK3 plays a role in promoting cell survival.
- WNK3 may regulate apoptosis through interaction with procaspase-3, influencing its activation.
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