ArticleThe Journal of biological chemistry2008
Sequential protein kinase C (PKC)-dependent and PKC-independent protein kinase D catalytic activation via Gq-coupled receptors: differential regulation of activation loop Ser(744) and Ser(748) phosphorylation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 86 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
- Protein Kinase D Plays a Crucial Role in Maintaining Cardiac Homeostasis by Regulating Post-Translational Modifications of Myofilament Proteins.International journal of molecular sciences · 2024Article
- 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
- Membrane trafficking in breast cancer progression: protein kinase D comes into play.Frontiers in cell and developmental biology · 2023Review
- Decoding the Cardiac Actions of Protein Kinase D Isoforms.Molecular pharmacology · 2021Review
- Review
- Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review.Lipids in health and disease · 2020Review
- Regulation of Osteoclast Differentiation at Multiple Stages by Protein Kinase D Family Kinases.International journal of molecular sciences · 2020Article
- A ubiquitin-like domain controls protein kinase D dimerization and activation by trans-autophosphorylation.The Journal of biological chemistry · 2019Article
- Protein kinase D and Gβγ mediate sustained nociceptive signaling by biased agonists of protease-activated receptor-2.The Journal of biological chemistry · 2019Article
- The CSN3 subunit of the COP9 signalosome interacts with the HD region of Sos1 regulating stability of this GEF protein.Oncogenesis · 2019Article
- Analysis of oncogenic activities of protein kinase D1 in head and neck squamous cell carcinoma.BMC cancer · 2018Article
- Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation.FEBS letters · 2018Article
- Protein kinase D signaling in cancer: A friend or foe?Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Protein kinase D1 (PKD1) phosphorylation on SerThe Journal of biological chemistry · 2017Article
- Androgen suppresses protein kinase D1 expression through fibroblast growth factor receptor substrate 2 in prostate cancer cells.Oncotarget · 2017Article
- A Conditional Knockout Mouse Model Reveals a Critical Role of PKD1 in Osteoblast Differentiation and Bone Development.Scientific reports · 2017Article
- Novel Small Molecule Inhibitors of Protein Kinase D Suppress NF-kappaB Activation and Attenuate the Severity of Rat Cerulein Pancreatitis.Frontiers in physiology · 2017Article
- Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System.Frontiers in pharmacology · 2017Review
- Phos-tag SDS-PAGE resolves agonist- and isoform-specific activation patterns for PKD2 and PKD3 in cardiomyocytes and cardiac fibroblasts.Journal of molecular and cellular cardiology · 2016Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase D (PKD) is a serine/threonine protein kinase rapidly activated by G protein-coupled receptor (GPCR) agonists via a protein kinase C (PKC)-dependent pathway. Recently, PKD has been implicated in the regulation of long term cellular activities, but little is known about the mechanism(s) of sustained PKD activation. Here, we show that cell treatment with the preferential PKC inhibitors GF 109203X or Gö 6983 blocked rapid (1-5-min) PKD activation induced by bombesin stimulation, but this inhibition was greatly diminished at later times of bombesin stimulation (e.g. 45 min). These results imply that GPCR-induced PKD activation is mediated by early PKC-dependent and late PKC-independent mechanisms. Western blot analysis with site-specific antibodies that detect the phosphorylated state of the activation loop residues Ser(744) and Ser(748) revealed striking PKC-independent phosphorylation of Ser(748) as well as Ser(744) phosphorylation that remained predominantly but not completely PKC-dependent at later times of bombesin or vasopressin stimulation (20-90 min). To determine the mechanisms involved, we examined activation loop phosphorylation in a set of PKD mutants, including kinase-deficient, constitutively activated, and PKD forms in which the activation loop residues were substituted for alanine. Our results show that PKC-dependent phosphorylation of the activation loop Ser(744) and Ser(748) is the primary mechanism involved in early phase PKD activation, whereas PKD autophosphorylation on Ser(748) is a major mechanism contributing to the late phase of PKD activation occurring in cells stimulated by GPCR agonists. The present studies identify a novel mechanism induced by GPCR activation that leads to late, PKC-independent PKD activation.
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Registered trials
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.