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- 저자 : MacNevin, Gillian (검색결과 2 건)
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Ye, Feng,Yang, Chansik,Kim, Jiyoon,MacNevin, Christopher J.,Hahn, Klaus M.,Park, Dongeun,Ginsberg, Mark H.,Kim, Chungho American Society for Biochemistry and Molecular Bi 2017 The Journal of biological chemistry Vol.292 No.24
<P>Epigallocatechin gallate (EGCG) is the principal bioactive ingredient in green tea and has been reported to have many health benefits. EGCG influences multiple signal transduction pathways related to human diseases, including redox, inflammation, cell cycle, and cell adhesion pathways. However, the molecular mechanisms of these varying effects are unclear, limiting further development and utilization of EGCG as a pharmaceutical compound. Here, we examined the effect of EGCG on two representative transmembrane signaling receptors, integrin alpha IIb beta 3 and epidermal growth factor receptor (EGFR). We report that EGCG inhibits talin-induced integrin alpha IIb beta 3 activation, but it activates alpha IIb beta 3 in the absence of talin both in a purified system and in cells. This apparent paradox was explained by the fact that the activation state of alpha IIb beta 3 is tightly regulated by the topology of beta 3 transmembrane domain (TMD); increases or decreases in TMD embedding can activate integrins. Talin increases the embedding of integrin beta 3 TMD, resulting in integrin activation, whereas we observed here that EGCG decreases the embedding, thus opposing talin-induced integrin activation. In the absence of talin, EGCG decreases the TMD embedding, which can also disrupt the integrin alpha-beta TMD interaction, leading to integrin activation. EGCG exhibited similar paradoxical behavior in EGFR signaling. EGCG alters the topology of EGFR TMD and activates the receptor in the absence of EGF, but inhibits EGF-induced EGFR activation. Thus, this widely ingested polyphenol exhibits pleiotropic effects on transmembrane signaling by modifying the topology of TMDs.</P>
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Pyle, Bryan W.,Tran, Hue T.,Pickel, Benjamin,Haslam, Tegan M.,Gao, Zhizeng,MacNevin, Gillian,Vederas, John C.,Kim, Soo‐,Un,Ro, Dae‐,Kyun Blackwell Publishing Ltd 2012 The FEBS journal Vol.279 No.17
<P>Valerian (<I>Valeriana</I> <I>officinalis</I>) is a popular medicinal plant in North America and Europe. Its root extract is commonly used as a mild sedative and anxiolytic. Among dozens of chemical constituents (e.g. alkaloids, iridoids, flavonoids, and terpenoids) found in valerian root, valerena‐4,7(11)‐diene and valerenic acid (C15 sesquiterpenoid) have been suggested as the active ingredients responsible for the sedative effect. However, the biosynthesis of the valerena‐4,7(11)‐diene hydrocarbon skeleton in valerian remains unknown to date. To identify the responsible terpene synthase, next‐generation sequencing (Roche 454 pyrosequencing) was used to generate ∼ 1 million transcript reads from valerian root. From the assembled transcripts, two sesquiterpene synthases were identified (<I>VoTPS1</I> and <I>VoTPS2</I>), both of which showed predominant expression patterns in root. Transgenic yeast expressing <I>VoTPS1</I> and <I>VoTPS2</I> produced germacrene C/germacrene D and valerena‐4,7(11)‐diene, respectively, as major terpene products. Purified VoTPS1 and VoTPS2 recombinant enzymes confirmed these activities <I>in vitro</I>, with competent kinetic properties (<I>K</I><SUB>m</SUB> of ∼ 10 μ<SMALL>m</SMALL> and <I>k</I><SUB>cat</SUB> of 0.01 s<SUP>−1</SUP> for both enzymes). The structure of the valerena‐4,7(11)‐diene produced from the yeast expressing <I>VoTPS2</I> was further substantiated by <SUP>13</SUP>C‐NMR and GC‐MS in comparison with the synthetic standard. This study demonstrates an integrative approach involving next‐generation sequencing and metabolically engineered microbes to expand our knowledge of terpenoid diversity in medicinal plants.</P><P><B>Database</B> The sequences of cDNAs described in this work are available in the GenBank database under the following accession numbers: VoTPS1, JQ437839; VoTPS2, JQ437840</P>
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