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Epigallocatechin gallate (EGCG) inhibits type II phosphatidylinositol 4-kinases: A key component in pathways of phosphoinositide turnover

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Title Epigallocatechin gallate (EGCG) inhibits type II phosphatidylinositol 4-kinases: A key component in pathways of phosphoinositide turnover
 
Creator SINHA, RK
PATEL, RY
BOJJIREDDY, N
DATTA, A
SUBRAHMANYAM, G
 
Subject PROSTATE CARCINOMA-CELLS
GREEN TEA POLYPHENOL
SPLENIC LYMPHOCYTES
SIGNAL-TRANSDUCTION
LUNG TUMORIGENESIS
GROWTH-INHIBITION
CROSS-LINKING
ZETA-CHAIN
(-)-EPIGALLOCATECHIN-3-GALLATE
CANCER
Phosphatidylinositol 4-kinase
Epigallocatechin gallate
T cell activation
Jurkat cells
 
Description Type II phosphatidylinositol (PtdIns) 4-kinases produce PtdIns 4-phosphate, an early key signaling molecule in phosphatidylinositol cycle, which is indispensable for T cell activation. Type II PtdIns 4-kinase alpha and beta have similar biochemical properties. To distinguish these isoforms Epigallocatechin gallate (EGCG) has been evaluated as a specific inhibitor. EGCG is the major active catechin in green tea having anti-inflammatory, antiatherogenic and cancer chemopreventive properties. The precise mechanism of actions and molecular targets of EGCG in early signaling cascades are not well understood. In the present study, we have shown that EGCG inhibits type II PtdIns 4-kinases (alpha and beta isoforms) and PtdIns 3-kinase activity in vitro. EGCG directly bind to both alpha and beta isoforms of type II PtdIns 4-kinases with a Kd of 2.62 mu M and 1.02 mu M, respectively. Type II PtdIns 4-kinase-EGCG complex have different binding pattern at its excited state. Both isoforms showed significant change in helicity upon binding with EGCG. EGCG modulates its effect by interacting with ATP binding pocket: the residues likely to be involved in EGCG binding were predicted by Autodock. Our findings suggest that EGCG inhibits two isoforms and could be a key to regulate T cell activation. Published by Elsevier Inc.
 
Publisher ELSEVIER SCIENCE INC
 
Date 2012-06-26T06:07:05Z
2012-06-26T06:07:05Z
2011
 
Type Article
 
Identifier ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,516(1)45-51
0003-9861
http://dx.doi.org/10.1016/j.abb.2011.09.005
http://dspace.library.iitb.ac.in/jspui/handle/100/14005
 
Language English