Involvement of phosphatidylinositol 3‐kinase in the activation of extracellular signal‐regulated kinase by PDGF in hepatic stellate cells

FEBS Letters

DeFranco, Raffaella¹  Pinzani, Massimo¹  Marra, Fabio¹  Laffi, Giacomo¹  Gentilini, Paolo¹ 

[1] Istituto di Medicina Interna, Università di Firenze Viale Morgagni 85, I-50134 Firenze, Italy

关键词: Extracellular signal-regulated kinase;    Phosphatidylinositol 3-kinase;    Wortmannin;    Hepatic stellate cell;    c-fos;    Mitogen-activated protein kinase;   

DOI  :  10.1016/0014-5793(95)01261-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown