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Molecular and Cellular Biology, September 2000, p. 6768-6778, Vol. 20, No. 18
Departments of Medical
Biophysics1 and Molecular and Medical
Genetics,2 University of Toronto, and
Ontario Cancer Institute,3 Toronto,
Ontario, Canada M5G 2M9; Department of Pediatrics, The Hospital
for Sick Children Research Institute, Toronto, Ontario, Canada M5G
1X85; Institute of Anatomy and Cell
Biology, Göteborg University, SE-405 30 Gothenburg,
Sweden4; and Department of Molecular
Biology, Cell Biology and Biochemistry, Brown University,
Providence, Rhode Island 029126
Received 9 May 2000/Accepted 19 June 2000
Platelet-derived growth factor BB (PDGF BB) is a potent mitogen for
fibroblasts as well as many other cell types. Interaction of PDGF BB
with the PDGF
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Myc Is an Essential Negative Regulator of
Platelet-Derived Growth Factor Beta Receptor Expression


receptor (PDGF-
R) activates numerous signaling
pathways and leads to a decrease in receptor expression on the cell
surface. PDGF-
R downregulation is effected at two levels, the
immediate internalization of ligand-receptor complexes and the
reduction in pdgf-
r mRNA expression. Our studies show that pdgf-
r mRNA suppression is regulated by the
c-myc proto-oncogene. Both constitutive and inducible
ectopic Myc protein can suppress pdgf-
r mRNA and
protein. Suppression of pdgf-
r mRNA in response to Myc
is specific, since expression of the related receptor
pdgf-
r is not affected. We further show that Myc
suppresses pdgf-
r mRNA expression by a mechanism
which is distinguishable from Myc autosuppression. Analysis of
c-Myc-null fibroblasts demonstrates that Myc is required for the
repression of pdgf-
r mRNA expression in quiescent
fibroblasts following mitogen stimulation. In addition, it is evident
that the Myc-mediated repression of pdgf-
r mRNA
levels plays an important role in the regulation of basal
pdgf-
r expression in proliferating cells. Thus, our
studies suggest an essential role for Myc in a negative-feedback loop
regulating the expression of the PDGF-
R.
*
Corresponding author. Mailing address: Division of
Cellular and Molecular Biology, Department of Medical Biophysics, 610 University Ave., Toronto, Ontario, Canada M5G 2M9. Phone: (416)
946-2276. Fax: (416) 946-2065. E-mail:
lpenn{at}oci.utoronto.ca.
Present address: Rodiumhemmet, Karolinska Sjukhuset, S-171 76 Stockholm, Sweden.
Present address: Department of Microbiology, The Hospital for Sick
Children Research Institute, Toronto, Ontario, Canada M5G 1X8.
§
Present address: The Montreal General Hospital Institute, Centre
for Research in Neurosciences, Montreal, Quebec, Canada H3G 1A4.
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