Epigallocatechin gallate has pleiotropic effects on transmembrane signaling by altering the embedding of transmembrane domains

Feng Ye, Chansik Yang, Jiyoon Kim, Christopher J. MacNevin, Klaus M. Hahn, Dongeun Park, Mark H. Ginsberg, Chungho Kim

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)9858-9864
Number of pages7
JournalJournal of Biological Chemistry
Volume292
Issue number24
DOIs
Publication statusPublished - 2017 Jun 16

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Talin
Integrins
Chemical activation
Epidermal Growth Factor Receptor
Topology
Epidermal Growth Factor
epigallocatechin gallate
Signal transduction
Cell adhesion
Polyphenols
Insurance Benefits
Tea
Cell Adhesion
Oxidation-Reduction
Signal Transduction
Cell Cycle
Cells
Health
Inflammation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Epigallocatechin gallate has pleiotropic effects on transmembrane signaling by altering the embedding of transmembrane domains. / Ye, Feng; Yang, Chansik; Kim, Jiyoon; MacNevin, Christopher J.; Hahn, Klaus M.; Park, Dongeun; Ginsberg, Mark H.; Kim, Chungho.

In: Journal of Biological Chemistry, Vol. 292, No. 24, 16.06.2017, p. 9858-9864.

Research output: Contribution to journalArticle

Ye, Feng ; Yang, Chansik ; Kim, Jiyoon ; MacNevin, Christopher J. ; Hahn, Klaus M. ; Park, Dongeun ; Ginsberg, Mark H. ; Kim, Chungho. / Epigallocatechin gallate has pleiotropic effects on transmembrane signaling by altering the embedding of transmembrane domains. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 24. pp. 9858-9864.
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