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Involvement of phosphatidylinositol 3‐kinase in the activation of extracellular signal‐regulated kinase by PDGF in hepatic stellate cells
Author(s) -
Marra Fabio,
Pinzani Massimo,
DeFranco Raffaella,
Laffi Giacomo,
Gentilini Paolo
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01261-0
Subject(s) - phosphatidylinositol , hepatic stellate cell , platelet derived growth factor receptor , kinase , chemistry , microbiology and biotechnology , extracellular , biochemistry , biology , endocrinology , growth factor , receptor
Phosphatidylinositol 3‐kinase (PI 3‐K) is a lipid and protein kinase which associates with the activated platelet‐derived growth factor (PDGF) receptor and other tyrosine kinases. We studied the effects of wortmannin, a selective inhibitor of PI 3‐K, on the activation of extracellular‐signal regulated kinase (ERK) by PDGF in cultured hepatic stellate cells, mesenchymal cells responsible for extracellular matrix synthesis within the liver. Incubation with 100 nM wortmannin, a dose which almost completely blocks PI 3‐K, resulted in 50% reduction of ERK activity. Direct inhibition of ERK by wortmannin could not be considered responsible for this effect, since wortmannin did not inhibit ERK activity in vitro. Rather, inhibition of PI 3‐K acts on the kinase cascade that leads to ERK activation, since PDGF‐dependent phosphorylation of ERK was found to be reduced after incubation with wortmannin. Wortmannin also inhibited the increase in c‐ fos mRNA induced by PDGF, which is dependent on ERK activation. The results of this study show that in hepatic stellate cells PI 3‐K is involved in ERK activation, although it is not necessary. These data indicate cross‐talk between PI 3‐K and the Ras/ERK pathway in PDGF‐stimulated cells.