Summary: To elucidate the intracellular signaling pathways for VLDL-induced VLDLR transcrip-tion, Western blot analysis was used to examine phosphorylated ERK1/2 protein. It was found thatthat VLDL induced an increase in ERK1/2 activity in a protein kinase C (PKG)-dependent mannerin murine RAW264.7 macrophages. By using different protein kinases inhibitors or activators it wasobserved that the effect of VLDL-induced VLDL receptor transcription, which is monitored by RT-PCR analysis of VLDL receptor mRNA, was not affected by the inhibitor of p38 kinase and cAMPanalog, but completely abolished by pretreatment of the cells with PD 98059, an inhibitor of MEKand GF 109203X, an inhibitor of PKC. These results demonstrated that the PKC/ERK1/2 cascadeis the essential signaling pathway by which VLDL activates VLDL receptor mRNA expression.