ArticleAmerican journal of physiology. Cell physiology2006
Protein kinase D protects against oxidative stress-induced intestinal epithelial cell injury via Rho/ROK/PKC-delta pathway activation.
Article in American journal of physiology. Cell physiology, 2006. 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, 59 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
- Pepducin ICL1-9-Mediated β2-Adrenergic Receptor-Dependent Cardiomyocyte Contractility Occurs in a GCardiovascular drugs and therapy · 2023Article
- Oxidative Stress in Cancer Cell Metabolism.Antioxidants (Basel, Switzerland) · 2021Review
- The tumor suppressor protein DLC1 maintains protein kinase D activity and Golgi secretory function.The Journal of biological chemistry · 2018Article
- Administration of Protein Kinase D1 Induces a Protective Effect on Lipopolysaccharide-Induced Intestinal Inflammation in a Co-Culture Model of Intestinal Epithelial Caco-2 Cells and RAW264.7 Macrophage Cells.International journal of inflammation · 2017Article
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- Protein kinase D regulates RhoA activity via rhotekin phosphorylation.The Journal of biological chemistry · 2012Article
- Protein kinase D1 maintains the epithelial phenotype by inducing a DNA-bound, inactive SNAI1 transcriptional repressor complex.PloS one · 2012Article
- Protein kinase D: coupling extracellular stimuli to the regulation of cell physiology.EMBO reports · 2011Review
- Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes.Oncogene · 2011Article
- Protein kinase D signaling: multiple biological functions in health and disease.Physiology (Bethesda, Md.) · 2011Review
- Role of protein kinase D signaling in pancreatic cancer.Biochemical pharmacology · 2010Review
- Revisited and revised: is RhoA always a villain in cardiac pathophysiology?Journal of cardiovascular translational research · 2010Review
- Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists.Molecular & cellular proteomics : MCP · 2010Article
- Efficient procurement of epithelial stem cells from human tissue specimens using a Rho-associated protein kinase inhibitor Y-27632.Tissue engineering. Part A · 2010Article
- Protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility through slingshot.Nature cell biology · 2009Article
- Loss of cell-cell contacts induces NF-kappaB via RhoA-mediated activation of protein kinase D1.Journal of cellular biochemistry · 2009Article
- PKD prevents H2O2-induced apoptosis via NF-kappaB and p38 MAPK in RIE-1 cells.Biochemical and biophysical research communications · 2009Article
- Protein kinase D1 regulates matrix metalloproteinase expression and inhibits breast cancer cell invasion.Breast cancer research : BCR · 2009Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase D (PKD) is a novel protein serine kinase that has recently been implicated in diverse cellular functions, including apoptosis and cell proliferation. The purpose of our present study was 1) to define the activation of PKD in intestinal epithelial cells treated with H2O2, an agent that induces oxidative stress, and 2) to delineate the upstream signaling mechanisms mediating the activation of PKD. We found that the activation of PKD is induced by H2O2 in both a dose- and time-dependent fashion. PKD phosphorylation was attenuated by rottlerin, a selective PKC-delta inhibitor, and by small interfering RNA (siRNA) directed against PKC-delta, suggesting the regulation of PKD activity by upstream PKC-delta. Activation of PKD was also blocked by a Rho kinase (ROK)-specific inhibitor, Y-27632, as well as by C3, a Rho protein inhibitor, demonstrating that the Rho/ROK pathway also mediates PKD activity in intestinal cells. In addition, H2O2-induced PKC-delta phosphorylation was inhibited by C3 treatment, further suggesting that PKC-delta is downstream of Rho/ROK. Interestingly, H2O2-induced intestinal cell apoptosis was enhanced by PKD siRNA. Together, these results clearly demonstrate that oxidative stress induces PKD activation in intestinal epithelial cells and that this activation is regulated by upstream PKC-delta and Rho/ROK pathways. Importantly, our findings suggest that PKD activation protects intestinal epithelial cells from oxidative stress-induced apoptosis. These findings have potential clinical implications for intestinal injury associated with oxidative stress (e.g., necrotizing enterocolitis in infants).
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