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Am J Physiol Cell Physiol 268: C1033-C1039, 1995;
0363-6143/95 $5.00
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AJP - Cell Physiology, Vol 268, Issue 4 C1033-C1039, Copyright © 1995 by American Physiological Society

ARTICLES

Isoform-specific induction of the low-density lipoprotein receptor gene by platelet-derived growth factor

C. Rechtoris and T. Mazzone
Department of Medicine, Rush Medical College, Chicago, Illinois 60612, USA.

We investigated the effect of recombinant platelet-derived growth factor (PDGF) isomers on low-density lipoprotein (LDL) receptor gene expression and compared this with two indexes of cell growth response: expression of the immediate early gene c-myc and the rate of DNA synthesis. In human skin fibroblasts and NIH 3T3 cells, the PDGF-BB homodimer was more effective in inducing the LDL receptor gene and cell growth response compared with the PDGF-AA homodimer. The second messenger pathways utilized by PDGF receptors for enhancing LDL receptor gene response could, however, be dissociated from those utilized for enhancing c-myc gene response and were insensitive to inhibitors of tyrosine phosphorylation. Inhibition of tyrosine kinase activity inhibited c-myc gene response to PDGF-BB at 10(-8) M but had little effect on LDL receptor gene response. Such inhibition increased expression of the LDL receptor gene in the presence of the PDGF-AA isomer. Our results indicate that the response of the LDL receptor gene to PDGF isoforms reflects cellular growth response. However, different transduction pathways are utilized for PDGF activation of the c-myc and LDL receptor genes in mesenchymal cells.


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