ArticleCellular signalling2012
Differential PKC-dependent and -independent PKD activation by G protein α subunits of the Gq family: selective stimulation of PKD Ser⁷⁴⁸ autophosphorylation by Gαq.
Article in Cellular signalling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Activation of the Piezo1 channel stimulates protein kinase D and migration in human aortic endothelial cells.American journal of physiology. Cell physiology · 2025Article
- Statins inhibit protein kinase D (PKD) activation in intestinal cells and prevent PKD1-induced growth of murine enteroids.American journal of physiology. Cell physiology · 2023Article
- Regulation of Osteoclast Differentiation at Multiple Stages by Protein Kinase D Family Kinases.International journal of molecular sciences · 2020Article
- Protein kinase D and Gβγ mediate sustained nociceptive signaling by biased agonists of protease-activated receptor-2.The Journal of biological chemistry · 2019Article
- Multifaceted regulation and functions of YAP/TAZ in tumors (Review).Oncology reports · 2018Review
- Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation.FEBS letters · 2018Article
- Protein kinase D1 (PKD1) phosphorylation on SerThe Journal of biological chemistry · 2017Article
- Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System.Frontiers in pharmacology · 2017Review
- Biphasic Regulation of Yes-associated Protein (YAP) Cellular Localization, Phosphorylation, and Activity by G Protein-coupled Receptor Agonists in Intestinal Epithelial Cells: A NOVEL ROLE FOR PROTEIN KINASE D (PKD).The Journal of biological chemistry · 2016Article
- Positive cross talk between protein kinase D and β-catenin in intestinal epithelial cells: impact on β-catenin nuclear localization and phosphorylation at Ser552.American journal of physiology. Cell physiology · 2016Article
- Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of non-ischaemic dilated cardiomyopathy.European heart journal · 2015Article
- β-adrenergic signaling inhibits Gq-dependent protein kinase D activation by preventing protein kinase D translocation.Circulation research · 2014Article
- The actions of Pasteurella multocida toxin on neuronal cells.Neuropharmacology · 2014Article
- Pasteurella multocida toxin (PMT) upregulates CTGF which leads to mTORC1 activation in Swiss 3T3 cells.Cellular signalling · 2013Article
- Gβγ-mediated activation of protein kinase D exhibits subunit specificity and requires Gβγ-responsive phospholipase Cβ isoforms.Cell communication and signaling : CCS · 2013Article
- No contribution of IP3-R(2) to disease phenotype in models of dilated cardiomyopathy or pressure overload hypertrophy.Circulation. Heart failure · 2013Article
- PKD1 mediates negative feedback of PI3K/Akt activation in response to G protein-coupled receptors.PloS one · 2013Article
- G protein-coupled receptor (GPR)40-dependent potentiation of insulin secretion in mouse islets is mediated by protein kinase D1.Diabetologia · 2012Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Protein kinase D (PKD) is activated within cells by stimulation of multiple G protein coupled receptors (GPCR). Earlier studies demonstrated a role for PKC to mediate rapid activation loop phosphorylation-dependent PKD activation. Subsequently, a novel PKC-independent pathway in response to Gαq-coupled GPCR stimulation was identified. Here, we examined further the specificity and PKC-dependence of PKD activation using COS-7 cells cotransfected with different Gq-family Gα and stimulated with aluminum fluoride (AlF4⁻). PKD activation was measured by kinase assays, and Western blot analysis of activation loop sites Ser⁷⁴⁴, a prominent and rapid PKC transphosphorylation site, and Ser⁷⁴⁸, a site autophosphorylated in the absence of PKC signaling. Treatment with AlF4⁻ potently induced PKD activation and Ser⁷⁴⁴ and Ser⁷⁴⁸ phosphorylation, in the presence of cotransfected Gαq, Gα11, Gα14 or Gα15. These treatments achieved PKD activation loop phosphorylation similar to the maximal levels obtained by stimulation with the phorbol ester, PDBu. Preincubation with the PKC inhibitor GF1 potently blocked Gα11-, Gα14-, and Gα15-mediated enhancement of Ser⁷⁴⁸ phosphorylation induced by AlF4⁻, and largely abolished Ser⁷⁴⁴ phosphorylation. In contrast, Ser⁷⁴⁸ phosphorylation was almost completely intact, and Ser⁷⁴⁴ phosphorylation was significantly activated in cells cotransfected with Gαq. Importantly, the differential Ser⁷⁴⁸ phosphorylation was also promoted by treatment of Swiss 3T3 cells with Pasteurella multocida toxin, a selective activator of Gαq but not Gα11. Taken together, our results suggest that Gαq, but not the closely related Gα11, promotes PKD activation in response to GPCR ligands in a unique manner leading to PKD autophosphorylation at Ser⁷⁴⁸.
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