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

Kyung-Sun Heo; Dong-Uk Kim; Lila Kim; Miyoung Nam; Seung-Tae Baek; Song-Kyu Park; Youngwoo Park; Chang-Seon Myung; Sung-Ook Hwang; Kwang-Lae Hoe

doi:10.1016/j.bbrc.2008.01.050

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

Biochem Biophys Res Commun. 2008 Mar 28;368(1):126-31. doi: 10.1016/j.bbrc.2008.01.050. Epub 2008 Jan 22.

Authors

Kyung-Sun Heo¹, Dong-Uk Kim, Lila Kim, Miyoung Nam, Seung-Tae Baek, Song-Kyu Park, Youngwoo Park, Chang-Seon Myung, Sung-Ook Hwang, Kwang-Lae Hoe

Affiliation

¹ Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong, Daejeon, Republic of Korea.

PMID: 18211822
DOI: 10.1016/j.bbrc.2008.01.050

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.

MeSH terms

Aorta / drug effects
Aorta / enzymology
Cell Line
Cell Membrane / drug effects
Cell Membrane / metabolism
Cell Proliferation / drug effects
Cholesterol, LDL / pharmacology*
Cytosol / drug effects
Cytosol / metabolism
Early Growth Response Protein 1 / metabolism*
Enzyme Activation / drug effects
Extracellular Signal-Regulated MAP Kinases / metabolism*
GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
Humans
Isoenzymes / metabolism*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Myocytes, Smooth Muscle / drug effects
Myocytes, Smooth Muscle / enzymology*
Protein Kinase C / metabolism*
Protein Kinase C beta
Protein Kinase C-theta
Protein Transport
Receptors, G-Protein-Coupled / metabolism
Up-Regulation / drug effects

Substances

Cholesterol, LDL
Early Growth Response Protein 1
Isoenzymes
Receptors, G-Protein-Coupled
PRKCQ protein, human
Protein Kinase C
Protein Kinase C beta
Protein Kinase C-theta
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
GTP-Binding Protein alpha Subunits, Gi-Go