We recently demonstrated that phospholipase D activation by sphingosine 1-phosphate regulates ERK1/2 activation and interleukin-8 secretion in human bronchial epithelial cells
2008
Protein Kinase C-ϵ Regulates Sphingosine 1-Phosphate-mediated Migration of Human Lung Endothelial Cells through Activation of Phospholipase D2, Protein Kinase C-ζ, and Rac1
Key concepts
- S1P2
- metastasis
- phosphatidylinositol 3-kinase
- growth factor
- lysophosphatidic acid
- platelet-derived growth factor
- S1P1
- phospholipase D
- phosphatidylinositol-4-phosphate 5-kinase
- PLD2
- Western blot
- epidermal growth factor
- protein kinase
- Endothelial cell
- fibroblast
- sphingosine 1-phosphate
- protein kinase C
- pertussis toxin
- angiogenesis
- S1P3
- S1P receptor
- sphingosine
- MAPK
- wound healing
- small interfering RNA
- guanine nucleotide exchange factor
- mitogen-activated protein kinases
Scholarcy highlights
- We investigated the role of protein kinase C isoforms, phospholipase D, and Rac in sphingosine 1-phosphate-induced migration of human pulmonary artery endothelial cells
- Our results show that physiologically relevant concentrations of sphingosine 1-phosphate markedly stimulated human pulmonary artery endothelial cells migration, which was sensitive to pertussis toxin and a S1P1 antagonist
- To obtain evidence that S1P1 is involved in S1P-induced cell migration and wound healing, we tested the ability of SB649146, which reduces constitutively active S1P1 and blocks S1P binding, on
- Several studies demonstrated a role for platelet-derived growth factor, vascular endothelial growth factor, and fibroblast growth factor as well as ECM-derived proteins such as fibronectin, vitronectin, collagen, and laminin in regulating Endothelial cell migration and angiogenesis
- We observed that S1P1 is the predominant S1P receptor expressed in HPAECs, which is coupled to Gi in transducing signals from S1P to intracellular targets such as phospholipase D
- The effect of vascular endothelial growth factor on Rac1-dependent motility of human umbilical vein ECs is regulated by Vav2 guanine nucleotide exchange factor, and our preliminary results show that S1P-induced Rac1 activation is partly dependent on Tiam1, another GEF for Rac1.4 the role of Tiam1 in PLD2-dependent regulation of Rac1 via protein kinase C- is unclear, and future studies will address the role of guanine nucleotide exchange factors in S1P-induced cell motility
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