ArticleThe Journal of biological chemistry2008
Protein kinase C-epsilon regulates sphingosine 1-phosphate-mediated migration of human lung endothelial cells through activation of phospholipase D2, protein kinase C-zeta, and Rac1.
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 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Multi-omics analyses of airway host-microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions.Nature microbiology · 2022Article
- Natural Compounds as Target Biomolecules in Cellular Adhesion and Migration: From Biomolecular Stimulation to Label-Free Discovery and Bioactivity-Based Isolation.Biomedicines · 2021Review
- Review
- Distinctive requirement of PKCε in the control of Rho GTPases in epithelial and mesenchymally transformed lung cancer cells.Oncogene · 2019Article
- In vitro cell migration quantification method for scratch assays.Journal of the Royal Society, Interface · 2019Article
- Cortical Actin Dynamics in Endothelial Permeability.Current topics in membranes · 2018Article
- Cysteinyl leukotrienes as novel host factors facilitating Cryptococcus neoformans penetration into the brain.Cellular microbiology · 2017Article
- Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells.Molecules (Basel, Switzerland) · 2017Review
- Prometastatic NEDD9 Regulates Individual Cell Migration via Caveolin-1-Dependent Trafficking of Integrins.Molecular cancer research : MCR · 2015Article
- Inhibited insulin signaling in mouse hepatocytes is associated with increased phosphatidic acid but not diacylglycerol.The Journal of biological chemistry · 2015Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Article
- Redundant role of protein kinase C delta and epsilon during mouse embryonic development.PloS one · 2014Article
- Loss of phosphatase and tensin homolog (PTEN) induces leptin-mediated leptin gene expression: feed-forward loop operating in the lung.The Journal of biological chemistry · 2013Article
- Atypical protein kinase C in cell motility.Cellular and molecular life sciences : CMLS · 2013Review
- Epidermal growth factor-induced cellular invasion requires sphingosine-1-phosphate/sphingosine-1-phosphate 2 receptor-mediated ezrin activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- The roles of sphingosine kinase 1 and 2 in regulating the metabolome and survival of prostate cancer cells.Biomolecules · 2013Article
- Coronin 1B regulates S1P-induced human lung endothelial cell chemotaxis: role of PLD2, protein kinase C and Rac1 signal transduction.PloS one · 2013Article
- Phospholipase D signaling mediates reactive oxygen species-induced lung endothelial barrier dysfunction.Pulmonary circulation · 2013Article
- Interplay between FAK, PKCδ, and p190RhoGAP in the regulation of endothelial barrier function.Microvascular research · 2012Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The signaling pathways by which sphingosine 1-phosphate (S1P) potently stimulates endothelial cell migration and angiogenesis are not yet fully defined. We, therefore, investigated the role of protein kinase C (PKC) isoforms, phospholipase D (PLD), and Rac in S1P-induced migration of human pulmonary artery endothelial cells (HPAECs). S1P-induced migration was sensitive to S1P(1) small interfering RNA (siRNA) and pertussis toxin, demonstrating coupling of S1P(1) to G(i). Overexpression of dominant negative (dn) PKC-epsilon or -zeta, but not PKC-alpha or -delta, blocked S1P-induced migration. Although S1P activated both PLD1 and PLD2, S1P-induced migration was attenuated by knocking down PLD2 or expressing dnPLD2 but not PLD1. Blocking PKC-epsilon, but not PKC-zeta, activity attenuated S1P-mediated PLD stimulation, demonstrating that PKC-epsilon, but not PKC-zeta, was upstream of PLD. Transfection of HPAECs with dnRac1 or Rac1 siRNA attenuated S1P-induced migration. Furthermore, transfection with PLD2 siRNA, infection of HPAECs with dnPKC-zeta, or treatment with myristoylated PKC-zeta peptide inhibitor abrogated S1P-induced Rac1 activation. These results establish that S1P signals through S1P(1) and G(i) to activate PKC-epsilon and, subsequently, a PLD2-PKC-zeta-Rac1 cascade. Activation of this pathway is necessary to stimulate the migration of lung endothelial cells, a key component of the angiogenic process.
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