title: Activation of PKCbeta(II) and PKCtheta is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation.
abstract: Native LDL may be a mitogenic stimulus of VSMC proliferation in lesions where endothelial disruption occurs. Recent studies have demonstrated that the mitogenic effects of LDL are accompanied by Erk1/2 activation via an unknown G-protein-coupled receptor (GPCR). In this article, we report that LDL translocated PKCbeta(II) and PKCtheta from cytosol to plasma membrane, and inhibition of PKCbeta(II) and PKCtheta decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKCbeta(II) and PKCtheta, suggesting that Gi protein plays a role in LDL effects. Of LPA, S1P, and LDL, whose signaling is conveyed via Gi/o proteins, only LDL induced translocation of PKCbeta(II) and PKCtheta. Inhibition of PKCbeta(II) or PKCtheta, as well as of Erk1/2 and GPCR, decreases LDL-induced upregulation of Egr-1, which is critical for cell proliferation. This is the first report, to our knowledge, that the participation of PKCtheta in VSMC proliferation is unique.
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong, Daejeon, Republic of Korea.
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Heo
authors.forename: Dong-Uk
authors.initials: DU
authors.lastname: Kim
authors.forename: Lila
authors.initials: L
authors.lastname: Kim
authors.forename: Miyoung
authors.initials: M
authors.lastname: Nam
authors.forename: Seung-Tae
authors.initials: ST
authors.lastname: Baek
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Youngwoo
authors.initials: Y
authors.lastname: Park
authors.forename: Chang-Seon
authors.initials: CS
authors.lastname: Myung
authors.forename: Sung-Ook
authors.initials: SO
authors.lastname: Hwang
authors.forename: Kwang-Lae
authors.initials: KL
authors.lastname: Hoe
mesh_terms: D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D008078:Cholesterol, LDL / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D000074121:Protein Kinase C-theta; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008078:Cholesterol, LDL; D051766:Early Growth Response Protein 1; D007527:Isoenzymes; D043562:Receptors, G-Protein-Coupled; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D000074121:Protein Kinase C-theta; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019206:GTP-Binding Protein alpha Subunits, Gi-Go