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PMID:23911909

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Citation

Kim, YH, Lee, SJ, Seo, KW, Bae, JU, Park, SY, Kim, EK, Bae, SS, Kim, JH and Kim, CD (2013) PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway. J. Lipid Res. 54:2678-86

Abstract

Platelet-activating factor (PAF), 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is a potent phospholipid mediator and has been reported to be localized in atherosclerotic plaque. However, its role in the progression of atherosclerosis remains unclear. In the present study, we investigated the role of PAF in the production of matrix metalloproteinase (MMP) in primary vascular smooth muscle cells (VSMCs). When rat aortic primary VSMCs were stimulated with PAF (1 nmol/l), the expressions of MMP-2 mRNA and protein, but not of MMP-9, were significantly increased, and these upregulations were markedly attenuated by inhibiting extracellular signal-regulated kinases (ERKs) using molecular and pharmacological inhibitors, but not by using inhibitors of p38 mitogen-activated protein kinase or c-Jun N-terminal kinase. Likewise, ERK phosphorylation was markedly enhanced in PAF-stimulated VSMCs, and this was attenuated by WEB2086, but not by EGF receptor inhibitor, demonstrating the specificity of PAF receptor (PAFR) in PAF-induced ERK phosphorylation. In immunofluorescence studies, β-arrestin2 in PAF-stimulated VSMCs colocalized with PAFR and phosphorylated ERK (P-ERK). Coimmunoprecipitation results suggest that β-arrestin2-bound PAFRs existed as a complex with P-ERK. In addition, PAF-induced ERK phosphorylation and MMP-2 production were significantly attenuated by β-arrestin2 depletion. Taken together, the study shows that PAF enhances MMP-2 production in VSMCs via a β-arrestin2-dependent ERK signaling pathway.

Links

PubMed PMC3770081 Online version:10.1194/jlr.M037176

Keywords

Animals; Aorta/cytology; Arrestins/metabolism; Cells, Cultured; Enzyme Induction; Extracellular Signal-Regulated MAP Kinases/metabolism; MAP Kinase Signaling System; Male; Matrix Metalloproteinase 2/metabolism; Muscle, Smooth, Vascular/cytology; Myocytes, Smooth Muscle/enzymology; Phosphorylation; Platelet Activating Factor/physiology; Platelet Membrane Glycoproteins/metabolism; Protein Processing, Post-Translational; Protein Transport; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:MMP2

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:PTAFR

enables

GO:0051019: mitogen-activated protein kinase binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:PTAFR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2157

F

Seeded From UniProt

complete

RAT:ARRB2

enables

GO:0031859: platelet activating factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:61897

F

Seeded From UniProt

complete

Notes

See also

References

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