Isoform-specific induction of the low density lipoprotein receptor gene by
platelet derived growth factor.
Rechtoris, Carol, and Theodore Mazzone.
Departments of Medicine and Biochemistry, Rush Medical College, Chicago,
Illinois 60612
APStracts 2:0012C, 1995.
We investigated the effect of recombinant PDGF isomers on LDL receptor gene
expression and compared this with two indices 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
to 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 10-8M 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.
Received 30 August 1994; accepted in final form 2 November 1994
APS Manuscript Number C0513-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.