Induction of very low density lipoprotein receptor (VLDLR) transcription by VLDL is mediated by the extracellular signal-regulated kinase signaling pathway.
To elucidate the intracellular signaling pathways for VLDL-induced VLDLR transcription, Western blot analysis was used to examine phosphorylated ERK1/2 protein. It was found that that VLDL induced an increase in ERK1/2 activity in a protein kinase C (PKC)-dependent manner in murine RAW264.7 macrophages. By using different protein kinases inhibitors or activators it was observed that the effect of VLDL-induced VLDL receptor transcription, which is monitored by RTPCR analysis of VLDL receptor mRNA, was not affected by the inhibitor of p38 kinase and cAMP analog, but completely abolished by pretreatment of the cells with PD 98059, an inhibitor of MEK and GF 109203X, an inhibitor of PKC. These results demonstrated that the PKC/ERK1/2 cascade is the essential signaling pathway by which VLDL activates VLDL receptor mRNA expression.
Wang
Yan
Y
Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030.
Qu
Shen
S
Zong
Yiqiang
Y
Zhang
Mingtao
M
Wu
Fan
F
D000818:Animals; D023081:CCAAT-Binding Factor / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D023081:CCAAT-Binding Factor; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D011973:Receptors, LDL; D014157:Transcription Factors; C036053:VLDL receptor; C402244:nuclear factor Y; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases