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J Biol Chem. 2017 Jun 16;292(24):9858-9864. doi: 10.1074/jbc.C117.787309. Epub 2017 May 9.

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

Author information

1
From the Department of Medicine, University of California San Diego School of Medicine, La Jolla, California 92093.
2
the Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
3
the School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea, and.
4
the Department of Pharmacology and Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
5
From the Department of Medicine, University of California San Diego School of Medicine, La Jolla, California 92093, mhginsberg@ucsd.edu.
6
the Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea, chungho@korea.ac.kr.

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, integrinαIIbβ3 and epidermal growth factor receptor (EGFR). We report that EGCG inhibits talin-induced integrin αIIbβ3 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 of αIIbβ3 is tightly regulated by the topology of β3 transmembrane domain (TMD); increases or decreases in TMD embedding can activate integrins. Talin increases the embedding of integrin β3 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 α-β 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.

KEYWORDS:

epidermal growth factor receptor (EGFR); integrin; polyphenol; talin; transmembrane domain

PMID:
28487468
PMCID:
PMC5473239
DOI:
10.1074/jbc.C117.787309
[Indexed for MEDLINE]
Free PMC Article

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