Inhibitors of Chymotrypsin-like Activities Selectively Block the Mitotic Pathway in Rat Hepatoma Cells
作者:
PonzioGilles,
OlivierJean,
DebantAnne,
AubergerPatrick,
FarahifarDariush,
RossiBernard,
期刊:
Growth Factors
(Taylor Available online 1990)
卷期:
Volume 4,
issue 1
页码: 37-44
ISSN:0897-7194
年代: 1990
DOI:10.3109/08977199009011008
出版商: Taylor&Francis
关键词: cell proliferation;protease inhibitors;insulin;FGF;tyrosine amino transferase;amino-acid transport
数据来源: Taylor
摘要:
AbstractWe provide evidence that both covalent and non-covalent inhibitors of chymotrypsin-like activities inhibit the insulin-induced DNA replication, while the hormonal metabolic effects such as induction of tyrosine aminotransferase activity or increase of amino-acid transport remain unchanged. Besides, the protease inhibitors that we tested were without any effect on both the autocatalytic phosphorylation of insulin receptors and the tyrosine kinase activity towards poly(glutamate/tyrosine). The inhibitory effect of protease inhibitors on DNA synthesis was also visible when fibroblast growth factor (FGF) was used to commit cells in the proliferative cycle. This observation proves that the involvement of a putative protease is not restricted to the insulin mitogenic pathway. Finally, we observed that Fao cells totally escaped the inhibitory action of a covalent inhibitor of chymotrypsin after having been exposed to insulin for 10 h. We propose that a chymotrypsin-like activity is involved in the intracellular signalling leading to the proliferation of rat hepatoma cells up to a non-return point situated in the middle of G1(6-8 h).
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