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KMID : 0578319960060040463
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Molecules and Cells
1996 Volume.6 No. 4 p.463 ~ p.468
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A Potent Inhibot of Platelet-derived Growth Factor Receptor Tyrosine Kinase
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Min, Do Sik
Lee, Young Han/kang, Lin Woo/Byoun, Chang-Hyoun/Chang, Song-Soo/Ryu, Sung Ho/suh, Pann-Ghill
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Abstract
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To find inhibitors that block the PDGF receptor-mediated mitogenic signal, we have established a screening system using NIH 3T3 cells (3T3-γ1) that overexpress PLC-γ1. The 3T3-γ1 cells formed 10 times more inositol phosphates than the control cells by PDGF treatment. Using this system, various herb extracts have been examined inhibitory effects for PDGF receptor mediated signalling. Among the medicinal plant extracts tested, the extract of Rhus javanica showed the highest level of inhibition and was selected as a source of potent inhibitory materials. The extract was fractionated with organic solvents and on C-18 HPLC column. Effects of the inhibitory fraction on the growth signal pathway was examined. The inhibitory effect of the fraction on the protein tyrosine kinase activity of the PDGF receptor correlated with inhibition of PDGF-dependent inositol phosphate formation and tyrosine phosphorylation of PLC-γ1. The inhibitory fraction, however, did not affect response to EGF in A431 cell, a ligand whose receptor also possesses intrinsic tyrosine kinase. These results suggest that the fraction from the extracts of Rhus javanica contains a specific inhibitor on PDGF-dependent growth signalling.
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