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J Biol Chem, Vol. 273, Issue 32, 20078-20083, August 7, 1998

The Granulin/Epithelin Precursor Abrogates the Requirement for the Insulin-like Growth Factor 1 Receptor for Growth in Vitro

Shi-Qiong XuDagger , Dazhi Tang§, Scott Chamberlain§, Gijsbertus Pronk§, Frank R. Masiarz, Surinder Kaur§, Marco PriscoDagger , Tommaso Zanocco-MaraniDagger , and Renato BasergaDagger

From the Dagger  Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, the § Chiron Corporation, Emeryville, California 94608, and the  Chiron Corporation and Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94608

3T3 cells null for the type 1 insulin-like growth factor receptor are refractory to stimulation by a variety of purified growth factors that are known to be required for the stimulation of other 3T3 cells. However, these cells, known as R- cells, grow in serum-supplemented medium and also in media conditioned by certain cell lines. We report here the purification of a growth factor that stimulates DNA synthesis (and growth) of R- cells. The growth factor, purified to homogeneity by SDS-polyacrylamide gel electrophoresis, was identified as the granulin/epithelin precursor by an accurate determination of the masses of endoproteinase Lys-C peptides using matrix-assisted laser desorption ionization mass spectrometry, followed by a data base search. The granulin/epithelin precursor is a little known growth factor, secreted by a variety of epithelial and hemopoietic cells. It is at present the only purified growth factor that can stimulate the growth of mouse embryo fibroblasts null for the type 1 insulin-like growth factor receptor.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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