ArticleThe Journal of biological chemistry2013
A phosphoinositide 3-kinase (PI3K)-serum- and glucocorticoid-inducible kinase 1 (SGK1) pathway promotes Kv7.1 channel surface expression by inhibiting Nedd4-2 protein.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain.Experimental neurology · 2024Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Quercetin is a foe in the heart by targeting the hERG potassium channel.Iranian journal of basic medical sciences · 2024Article
- The cellular pathways that maintain the quality control and transport of diverse potassium channels.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- A High-Throughput Screening Assay to Identify Drugs that Can Treat Long QT Syndrome Caused by Trafficking-Deficient KMolecular pharmacology · 2022Article
- MTMR4 SNVs modulate ion channel degradation and clinical severity in congenital long QT syndrome: insights in the mechanism of action of protective modifier genes.Cardiovascular research · 2021Article
- The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels.Frontiers in pharmacology · 2019Article
- Regulation of Kv1.4 potassium channels by PKC and AMPK kinases.Channels (Austin, Tex.) · 2018Article
- Inhibition of serum and glucocorticoid regulated kinase-1 as novel therapy for cardiac arrhythmia disorders.Scientific reports · 2017Article
- SGK1: The Dark Side of PI3K Signaling.Current topics in developmental biology · 2017Review
- A novel missense mutation in the C2C domain of otoferlin causes profound hearing impairment in an Omani family with auditory neuropathy.Saudi medical journal · 2016Article
- Ubiquitin ligase Nedd4-2 modulates Kv1.3 current amplitude and ion channel protein targeting.Journal of neurophysiology · 2016Article
- Fundamental role for the KCNE4 ancillary subunit in Kv7.4 regulation of arterial tone.The Journal of physiology · 2015Article
- Phosphoinositide dependent protein kinase 1 is required for exercise-induced cardiac hypertrophy but not the associated mitochondrial adaptations.Journal of molecular and cellular cardiology · 2015Article
- Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking.American journal of physiology. Cell physiology · 2015Article
- Control of cardiac repolarization by phosphoinositide 3-kinase signaling to ion channels.Circulation research · 2015Review
- PKC and AMPK regulation of Kv1.5 potassium channels.Channels (Austin, Tex.) · 2015Article
- Klotho: a new trafficking modifier of Kv7.1/KCNE1 channels.Channels (Austin, Tex.) · 2014Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial cell polarization involves several kinase signaling cascades that eventually divide the surface membrane into an apical and a basolateral part. One kinase, which is activated during the polarization process, is phosphoinositide 3-kinase (PI3K). In MDCK cells, the basolateral potassium channel Kv7.1 requires PI3K activity for surface-expression during the polarization process. Here, we demonstrate that Kv7.1 surface expression requires tonic PI3K activity as PI3K inhibition triggers endocytosis of these channels in polarized MDCK. Pharmacological inhibition of SGK1 gave similar results as PI3K inhibition, whereas overexpression of constitutively active SGK1 overruled it, suggesting that SGK1 is the primary downstream target of PI3K in this process. Furthermore, knockdown of the ubiquitin ligase Nedd4-2 overruled PI3K inhibition, whereas a Nedd4-2 interaction-deficient Kv7.1 mutant was resistant to both PI3K and SGK1 inhibition. Altogether, these data suggest that a PI3K-SGK1 pathway stabilizes Kv7.1 surface expression by inhibiting Nedd4-2-dependent endocytosis and thereby demonstrates that Nedd4-2 is a key regulator of Kv7.1 localization and turnover in epithelial cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.