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  • Title: Inhibition of PDGF-induced phosphoinositide-turnover by glucopiericidin A.
    Author: Ahn SC, Kim BY, Park CS, Lee HS, Suh PG, Ryu SH, Rho HM, Rhee JS, Mheen TI, Ahn JS.
    Journal: Biochem Mol Biol Int; 1995 Sep; 37(1):125-32. PubMed ID: 8653074.
    Abstract:
    In the search for a substance which would specifically block a particular step in the signal transduction cascade, we identified glucopiericidin A produced by Streptomyces sp. as an inhibitor of phosphoinositide (PI)-turnover in phospholipase-Cgamma1 (PLC-gamma1) overexpressing NIH 3T3 fibroblasts (NIH 3T3gamma1). Glucopiericidin A inhibited the formation of inositol phosphate (IPt) in platelet-derived growth factor (PDGF)-stimulated NIH 3T3gamma1 cells with an IC50 of 5.0 microM. In vitro enzyme assay showed the compound had no inhibitory effect on PLC-gamma1 even at 100 microM concentration. Glucopiericidin A reduced PDGF-induced tyrosine phosphorylations of proteins, including PDGF receptor and PLC-gamma1, in the cells. In contrast, glucopiericidin A showed only a slight inhibitory effect on epidermal growth factor (EGF)-induced IPt production and protein tyrosine phosphorylations in A431 cells. These results suggest that glucopiericidin A inhibits PDGF-induced activation of PLC-gamma1 by reducing the tyrosine kinase activity of the PDGF receptor and it more potently inhibits PI-turnover induced by PDGF than by EGF.
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