Abstract
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 αIIbβ3 and epidermal growth factor receptor (EGFR). We report that EGCG inhibits talin-induced integrinαIIbβ3 activation, but it activates αIIbβ3 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 ofαIIbβ3 is tightly regulated by the topology ofβ3 transmembrane domain (TMD); increases or decreases in TMD embedding can activate integrins. Talin increases the embedding of integrinβ3 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 integrinα-β TMDinteraction, 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.
Original language | English |
---|---|
Pages (from-to) | 9858-9864 |
Number of pages | 7 |
Journal | Journal of Biological Chemistry |
Volume | 292 |
Issue number | 24 |
DOIs | |
Publication status | Published - 2017 Jun 16 |
Bibliographical note
Publisher Copyright:© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology