ArticleThe Journal of biological chemistry2011
cAMP activates TRPC6 channels via the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)-mitogen-activated protein kinase kinase (MEK)-ERK1/2 signaling pathway.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- Multifaceted roles of Epac signaling in renal functions.The Biochemical journal · 2025Review
- Pharmacotherapeutic Approaches to Treatment of Muscular Dystrophies.Biomolecules · 2023Review
- Role of adenosine A2a receptor in cancers and autoimmune diseases.Immunity, inflammation and disease · 2023Review
- TRPC3 Regulates Islet Beta-Cell Insulin Secretion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy.International journal of molecular sciences · 2023Review
- Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery.British journal of pharmacology · 2023Article
- Pharmacological TRPC6 inhibition improves survival and muscle function in mice with Duchenne muscular dystrophy.JCI insight · 2022Article
- Expression of canonical transient receptor potential channels in U-2 OS and MNNG-HOS osteosarcoma cell lines.Oncology letters · 2021Article
- The seed ofPharmaceutical biology · 2020Article
- TRPP2 and STIM1 form a microdomain to regulate store-operated CaCell communication and signaling : CCS · 2020Article
- CaCold Spring Harbor perspectives in biology · 2020Review
- RNA-seq analysis reveals TRPC genes to impact an unexpected number of metabolic and regulatory pathways.Scientific reports · 2020Article
- TRPC6-dependent CaCell death & disease · 2020Article
- Review
- ENKUR Is Involved in the Regulation of Cellular Biology in Colorectal Cancer Cells via PI3K/Akt Signaling Pathway.Technology in cancer research & treatment · 2019Article
- Novel Mechanisms for IGF-I Regulation by Glucagon in Carp Hepatocytes: Up-Regulation of HNF1α and CREB Expression via Signaling Crosstalk for IGF-I Gene Transcription.Frontiers in endocrinology · 2019Article
- Noradrenaline up-regulates volume-regulated chloride current by PKA-independent cAMP/exchange protein activated by cAMP pathway in human atrial myocytes.British journal of pharmacology · 2018Article
- Trpc6 inactivation confers protection in a model of severe nephrosis in rats.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Permeation and Rectification in Canonical Transient Receptor Potential-6 (TRPC6) Channels.Frontiers in physiology · 2018Review
- The human transient receptor potential vanilloid 3 channel is sensitized via the ERK pathway.The Journal of biological chemistry · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
cAMP is an important second messenger that executes diverse physiological function in living cells. In this study, we investigated the effect of cAMP on canonical TRPC6 (transient receptor potential channel 6) channels in TRPC6-expressing HEK293 cells and glomerular mesangial cells. The results showed that 500 μm 8-Br-cAMP, a cell-permeable analog of cAMP, elicited [Ca(2+)](i) increases and stimulated a cation current at the whole-cell level in TRPC6-expressing HEK293 cells. The effect of cAMP diminished in the presence of the PI3K inhibitors wortmannin and LY294002 or the MEK inhibitors PD98059, U0126, and MEK inhibitor I. 8-Br-cAMP also induced phosphorylation of MEK and ERK1/2. Conversion of serine to glycine at an ERK1/2 phosphorylation site (S281G) abolished the cAMP activation of TRPC6 as determined by whole-cell and cell-attached single-channel patch recordings. Experiments based on a panel of pharmacological inhibitors or activators suggested that the cAMP action on TRPC6 was not mediated by PKA, PKG, or EPAC (exchange protein activated by cAMP). Total internal fluorescence reflection microscopy showed that 8-Br-cAMP did not alter the trafficking of TRPC6 to the plasma membrane. We also found that, in glomerular mesangial cells, glucagon-induced [Ca(2+)](i) increases were mediated through the cAMP-PI3K-PKB-MEK-ERK1/2-TRPC6 signaling pathway. In summary, this study uncovered a novel TRPC6 activation mechanism in which cAMP activates TRPC6 via the PI3K-PKB-MEK-ERK1/2 signaling pathway.
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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.