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
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Creator |
SINHA, RK
PATEL, RY BOJJIREDDY, N DATTA, A SUBRAHMANYAM, G |
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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 |
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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.
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Publisher |
ELSEVIER SCIENCE INC
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Date |
2012-06-26T06:07:05Z
2012-06-26T06:07:05Z 2011 |
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Type |
Article
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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 |
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Language |
English
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