Related Experiment Video
Updated: Jul 27, 2026

09:18
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.
Oncogene
|February 28, 2006
Summary
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.
Related Concept Videos
Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...

