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J Biol Chem, Vol. 273, Issue 33, 21342-21351, August 14, 1998
From the Trauma Research Program and Department of Laboratory
Medicine and Pathobiology, Sunnybrook Health Science Centre, University
of Toronto, Toronto, Ontario M4N 3M5, Canada
Versican is a member of the large aggregating
chondroitin sulfate proteoglycan family. We have expressed in NIH3T3
fibroblasts a recombinant versican mini-gene comprising the G1 and G3
domains and 15% of the CS domain. We observed that expression of the
mini-versican gene stimulated cell proliferation as determined by cell
counting and cell cycle analysis. Addition of exogenous mini-versican
protein to cultured cells produced the same result. The effects of the mini-versican were greatly reduced when the G3 domain was deleted. Expression of the G3 domain alone promotes cell proliferation, and
addition of purified G3 gene products to NIH3T3 fibroblasts and
cultured chicken fibroblasts enhances cell growth. Further, deletion of
the epidermal growth factor (EGF)-like motifs in the versican G3 domain
reduced the effects of the mini-versican on cell proliferation. In the
presence of the purified mini-versican protein, antisense
oligonucleotides to the EGF receptor inhibited proliferation of NIH3T3
fibroblasts, compared with control sense oligonucleotides. Taken
together, these results imply that versican enhances cell
proliferation, and this effect is mediated, at least in part, by the
action of versican EGF-like motifs on endogenous EGF receptor.
The G3 Domain of Versican Enhances Cell Proliferation via
Epidermial Growth Factor-like Motifs
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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