ArticleThe Journal of biological chemistry2010
Protein kinase C-dependent phosphorylation of transient receptor potential canonical 6 (TRPC6) on serine 448 causes channel inhibition.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Impact of C-Terminal PKC Phosphorylation on TRPC6 Current Kinetics.International journal of molecular sciences · 2025Article
- Photoswitchable TRPC6 channel activators evoke distinct channel kinetics reflecting different gating behaviors.iScience · 2024Article
- Delineating Zinc Influx Mechanisms during Platelet Activation.International journal of molecular sciences · 2023Article
- α1-Adrenergic Stimulation Increases Platelet Adhesion to Endothelial Cells Mediated by TRPC6.Advances in experimental medicine and biology · 2023Article
- TRPC6 N338S is a gain-of-function mutant identified in patient with doxorubicin-induced cardiotoxicity.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- PKC regulation of ion channels: The involvement of PIPThe Journal of biological chemistry · 2022Review
- Sox9 is involved in the thyroid differentiation program and is regulated by crosstalk between TSH, TGFβ and thyroid transcription factors.Scientific reports · 2022Article
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- The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.Frontiers in cellular neuroscience · 2020Review
- Role of Transient Receptor Potential Canonical Channel 6 (TRPC6) in Diabetic Kidney Disease by Regulating Podocyte Actin Cytoskeleton Rearrangement.Journal of diabetes research · 2020Review
- Role of TRPC6 in Progression of Diabetic Kidney Disease.Current hypertension reports · 2019Review
- Proline-dependent and basophilic kinases phosphorylate human TRPC6 at serine 14 to control channel activity through increased membrane expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Phosphorylation of residues inside the SNARE complex suppresses secretory vesicle fusion.The EMBO journal · 2016Article
- Inhibition of TRPC6 by protein kinase C isoforms in cultured human podocytes.Journal of cellular and molecular medicine · 2015Article
- Transient receptor potential ion channels in primary sensory neurons as targets for novel analgesics.British journal of pharmacology · 2014Review
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- PLC-mediated PI(4,5)P2 hydrolysis regulates activation and inactivation of TRPC6/7 channels.The Journal of general physiology · 2014Article
- Nuclear factor κB mediates suppression of canonical transient receptor potential 6 expression by reactive oxygen species and protein kinase C in kidney cells.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
TRPC6 is a cation channel in the plasma membrane that plays a role in Ca(2+) entry following the stimulation of a G(q)-protein coupled or tyrosine kinase receptor. A dysregulation of TRPC6 activity causes abnormal proliferation of smooth muscle cells and glomerulosclerosis. In the present study, we investigated the regulation of TRPC6 activity by protein kinase C (PKC). We showed that inhibiting PKC with GF1 or activating it with phorbol 12-myristate 13-acetate potentiated and inhibited agonist-induced Ca(2+) entry, respectively, into cells expressing TRPC6. Similar results were obtained when TRPC6 was directly activated with 1-oleyl-2-acetyl-sn-glycerol. Activation of the cells with carbachol increased the phosphorylation of TRPC6, an effect that was prevented by the inhibition of PKC. The target residue of PKC was identified by an alanine screen of all canonical PKC sites on TRPC6. Unexpectedly, all the mutants, including TRPC6(S768A) (a residue previously proposed to be a target for PKC), displayed PKC-dependent inhibition of channel activity. Phosphorylation prediction software suggested that Ser(448), in a non-canonical PKC consensus sequence, was a potential target for PKCδ. Ba(2+) and Ca(2+) entry experiments revealed that GF1 did not potentiate TRPC6(S448A) activity. Moreover, activation of PKC did not enhance the phosphorylation state of TRPC6(S448A). Using A7r5 vascular smooth muscle cells, which endogenously express TRPC6, we observed that a novel PKC isoform is involved in the inhibition of the vasopressin-induced Ca(2+) entry. Furthermore, knocking down PKCδ in A7r5 cells potentiated vasopressin-induced Ca(2+) entry. In summary, we provide evidence that PKCδ exerts a negative feedback effect on TRPC6 through the phosphorylation of Ser(448).
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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.