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Title 

Inhibition of PDGF-induced phosphoinositide turnover by glucopiercidin A

Authors 

Soon Cheol AhnBo Yeon KimChan Sun ParkHyun Sun LeePan Ghill SuhSung Ho RyuHyune Mo RhoJ S RheeTae Ick MheenJong Seog Ahn

Publisher 

International Union of Biochemistry and Molecular Biology

Issue Date 

1995

Citation 

Biochemistry and Molecular Biology International, vol. 37, no. 1, pp. 125-132

Keywords 

EGFglucopiericidin APDGFphosphoinositide-turnoverphospholipase Cγ1phosphoinositide metabolism

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-Cγ1 (PLC-γ1) overexpressing NIH 3T3 fibroblasts (NIH 3T3γ1). Glucopiericidin A inhibited the formation of inositol phosphate (IP(t)) in platelet-derived growth factor (PDGF)-stimulated NIH 3T3γ1 cells with an IC50 of 5.0 μM. In vitro enzyme assay showed the compound had no inhibitory effect on PLC-γ1 even at 100 μM concentration. Glucopiericidin A reduced PDGF-induced tyrosine phosphorylations of proteins, including PDGF receptor and PLC-γ1, in the cells. In contrast, glucopiericidin A showed only a slight inhibitory effect on epidermal growth factor (EGF)-induced IP(t) production and protein tyrosine phosphorylations in A431 cells. These results suggest that glucopiericidin A inhibits PDGF-induced activation of PLC-γ1 by reducing the tyrosine kinase activity of the PDGF receptor and it more potently inhibits PI-turnover induced by PDGF than by EGF.

ISSN 

1039-9712

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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