Activation of PKCb sub(I) sub(I) and PKCq is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation

• Published in: Biochemical and biophysical research communications Vol. 368; no. 1; pp. 126 - 131
• Main Authors: Heo, K S, Kim, DU, Kim, L, Nam, M, Baek, ST, Park, S K, Park, Y, Myung, C S, Hwang, SO, Hoe, K L
• Format: Journal Article
• Language: English
• Published: 28.03.2008
• ISSN: 0006-291X
• DOI: 10.1016/j.bbrc.2008.01.050

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 PKCb sub(I) sub(I) and PKCq from cytosol to plasma membrane, and inhibition of PKCb sub(I) sub(I) and PKCq decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKCb sub(I) sub(I) and PKCq, 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 PKCb sub(I) sub(I) and PKCq. Inhibition of PKCb sub(I) sub(I) or PKCq, 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 PKCq in VSMC proliferation is unique.