ID 47262
Title Transcription
ヒト サイタイ ジョウミャク ナイヒ サイボウ HUVEC ニオケル Lysophosphatidylcholine LPC シゲキ ニヨル VEGF レセプター ノ トランス アクチベーション
Title Alternative
Lysophosphatidylcholine (LPC) transactivates vascular endothelial growth factor (VEGF) receptor via c-Src in HUVEC
Author
Fujita, Yoshiko Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School
Yoshizumi, masanori Department of Pharmacology, Nara Medical University School of Medicine
Izawa, Yuki Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School
Kanematsu, Yasuhisa Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Tamaki, Toshiaki Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
LPC
endothelial cells
Flk-1/KDR
c-Src
atherosclerosis
Content Type
Journal Article
Description
One of the major lipid components of oxidized low density lipoprotein, lysophosphatidylcholine (LPC) is involved in numerous biological processes as a bioactive lipid molecule and has been shown to be involved in the progression of atherosclerosis. As counter-ligands, G2A and GPR4 were identified with high binding affinity for LPC that are belonging to orphan G-protein-coupled receptors (GPCRs) at plasma membranes. Although several GPCR ligands transactivate receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor, transactivation of RTK by LPC has not yet been reported. Here we observed for the first time that LPC treatment induces tyrosyl phosphorylation of vascular endothelial growth factor (VEGF) receptor2 (fetal liver kinase-1/kinase-insert domain-containing receptor, Flk-1/KDR) in human umbilical vein endothelial cells (HUVEC). VEGF receptor tyrosine kinase inhibitors, SU1498 and VTKi inhibited Flk-1/KDR transactivation by LPC. Furthermore, we examined the effect of the Src family kinases inhibitors, Herbimycin A and PP2 on LPC-induced Flk-1/KDR transactivation. Herbimycin A and PP2 inhibited Flk-1/KDR transactivation in HUVEC, suggesting that c-Src is involved in LPC-induced Flk-1/KDR transactivation. Kinase-inactive (KI) Src transfection also inhibited LPC-induced Flk-1/KDR transactivation. In addition, LPC activated extracellular signal-regulated kinase1/2 and Akt, which are downstream effectors of Flk-1/KDR, and these were inhibited by SU1498,VTKi, Herbimycin A, PP2 and KI Src transfection in HUVEC. LPC-mediated HUVEC proliferation was shown to be secondary to transactivation because it was suppressed by SU1498,VTKi, Herbimycin A, PP2and KI Src transfection. It is concluded that c-Src-mediated Flk-1/KDR transactivation by LPC may have important implications for the progression of atherosclerosis.
Journal Title
四国医学雑誌
ISSN
00373699
NCID
AN00102041
Publisher
徳島医学会
Volume
61
Issue
3-4
Start Page
91
End Page
94
Sort Key
91
Published Date
2005-08-25
Remark
EDB ID
FullText File
language
jpn
departments
University Hospital
Medical Sciences