Related Experiment Video

Updated: Apr 25, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

18.0K

WNK1 activates large-conductance Ca2+-activated K+ channels through modulation of ERK1/2 signaling

Yingli Liu1, Xiang Song2, Yanling Shi3

  • 1Renal Division, Department of Medicine, and Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine;

Journal of the American Society of Nephrology : JASN
|August 23, 2014
PubMed

Insights

With no lysine 1 (WNK1) enhances kidney large-conductance Ca(2+)-activated K(+) (BK) channel function. WNK1 reduces ERK1/2 signaling, preventing BK channel lysosomal degradation and increasing its expression.

Area of Science:

  • Molecular Biology
  • Renal Physiology
  • Ion Channel Regulation

Background:

  • With no lysine (WNK) kinases are serine/threonine kinases.
  • WNK4 was previously shown to inhibit renal large-conductance Ca(2+)-activated K(+) (BK) channel activity via lysosomal degradation.
  • The role of WNK1 in BK channel regulation remained unclear.

Purpose of the Study:

  • To investigate the effect of WNK1 on BK channel activity and expression.
  • To elucidate the molecular mechanisms underlying WNK1's regulation of BK channels.

Main Methods:

  • HEK293 cells stably expressing BKα subunits were used.
  • siRNA-mediated knockdown and overexpression of WNK1 were performed.
  • ERK1/2 phosphorylation, BKα protein expression, ubiquitination, and lysosomal degradation were assessed.
  • A high-potassium diet mouse model was utilized.

Main Results:

  • WNK1 knockdown inhibited BKα channel activity, open probability, and protein expression.
  • WNK1 knockdown increased ERK1/2 phosphorylation, while WNK1 overexpression decreased it.
  • ERK1/2 knockdown prevented WNK1 siRNA-induced inhibition of BKα expression.
  • Lysosomal inhibition reversed WNK1 siRNA-mediated effects on BKα expression.
  • WNK1 knockdown increased BKα ubiquitination.
  • High-K+ diet increased renal BKα and WNK1, and decreased ERK1/2 phosphorylation.

Conclusions:

  • WNK1 enhances BK channel function by inhibiting ERK1/2 signaling.
  • This inhibition reduces lysosomal degradation of BK channels, increasing their expression and activity.
  • WNK1 plays a significant role in regulating renal BK channel function, particularly in response to potassium intake.
Keywords:
Cell and transport physiologyK channelscell signaling

More Related Videos

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

2.3K
Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors10:59

Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors

Published on: February 10, 2014

9.5K

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
4.9K
MAPK Signaling Cascades01:07

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...
7.3K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.4K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
6.4K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

1.5K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
7.3K