ArticleScience signaling2019
The kinase PKD3 provides negative feedback on cholesterol and triglyceride synthesis by suppressing insulin signaling.
Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting PRKCN, an Essential Driver Orchestrating mTOR-IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chronic Aroclor 1260 exposure alters the mouse liver proteome, selenoproteins, and metals in steatotic liver disease.Environmental toxicology and pharmacology · 2024Article
- Integrated analysis of muscle lncRNA and mRNA of Chinese indigenous breed Ningxiang pig in four developmental stages.Frontiers in veterinary science · 2024Article
- Platelet-derived lipids promote insulin secretion of pancreatic β cells.EMBO molecular medicine · 2023Article
- The Transition of Cardiovascular Disease Risks from NAFLD to MAFLD.Reviews in cardiovascular medicine · 2023Review
- Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration.Cells · 2023Article
- Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus.Clinical medicine insights. Endocrinology and diabetes · 2023Article
- Dysregulated lipolysis and lipophagy in lipid droplets of macrophages from high fat diet-fed obese mice.Journal of cellular and molecular medicine · 2022Article
- DR1 Activation Inhibits the Proliferation of Vascular Smooth Muscle Cells through Increasing Endogenous HAging and disease · 2022Article
- A phosphoproteomic approach reveals that PKD3 controls PKA-mediated glucose and tyrosine metabolism.Life science alliance · 2021Article
- Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity.EMBO molecular medicine · 2021Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Small-Molecule Inhibitor Targeting Protein Kinase D: A Potential Therapeutic Strategy.Frontiers in oncology · 2021Review
- Metabolomics in postmortem cerebrospinal fluid diagnostics: a state-of-the-art method to interpret central nervous system-related pathological processes.International journal of legal medicine · 2021Article
- Loss of protein kinase D activity demonstrates redundancy in cardiac glucose metabolism and preserves cardiac function in obesity.Molecular metabolism · 2020Article
- Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice.Hepatology (Baltimore, Md.) · 2020Article
- Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review.Lipids in health and disease · 2020Review
- The adrenergic-induced ERK3 pathway drives lipolysis and suppresses energy dissipation.Genes & development · 2020Article
- Lipin1 Is Involved in the Pathogenesis of Diabetic Encephalopathy through the PKD/Limk/Cofilin Signaling Pathway.Oxidative medicine and cellular longevity · 2020Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Hepatic activation of protein kinase C (PKC) isoforms by diacylglycerol (DAG) promotes insulin resistance and contributes to the development of type 2 diabetes (T2D). The closely related protein kinase D (PKD) isoforms act as effectors for DAG and PKC. Here, we showed that PKD3 was the predominant PKD isoform expressed in hepatocytes and was activated by lipid overload. PKD3 suppressed the activity of downstream insulin effectors including the kinase AKT and mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2). Hepatic deletion of PKD3 in mice improved insulin-induced glucose tolerance. However, increased insulin signaling in the absence of PKD3 promoted lipogenesis mediated by SREBP (sterol regulatory element-binding protein) and consequently increased triglyceride and cholesterol content in the livers of PKD3-deficient mice fed a high-fat diet. Conversely, hepatic-specific overexpression of a constitutively active PKD3 mutant suppressed insulin-induced signaling and caused insulin resistance. Our results indicate that PKD3 provides feedback on hepatic lipid production and suppresses insulin signaling. Therefore, manipulation of PKD3 activity could be used to decrease hepatic lipid content or improve hepatic insulin sensitivity.
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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.