TY - JOUR
T1 - Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site
AU - Xu, Jinbin
AU - Zeng, Chenbo
AU - Chu, Wenhua
AU - Pan, Fenghui
AU - Rothfuss, Justin M.
AU - Zhang, Fanjie
AU - Tu, Zhude
AU - Zhou, Dong
AU - Zeng, Dexing
AU - Vangveravong, Suwanna
AU - Johnston, Fabian
AU - Spitzer, Dirk
AU - Chang, Katherine C.
AU - Hotchkiss, Richard S.
AU - Hawkins, William G.
AU - Wheeler, Kenneth T.
AU - MacH, Robert H.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2011
Y1 - 2011
N2 - The sigma-2 receptor, whose gene remains to be cloned, has been validated as a biomarker for tumour cell proliferation. Here we report the use of a novel photoaffinity probe, WC-21, to identify the sigma-2 receptor-binding site. WC-21, a sigma-2 ligand containing both a photoactive azide moiety and a fluorescein isothiocyanate group, irreversibly labels sigma-2 receptors in rat liver; the membrane-bound protein was identified as PGRMC1 (progesterone receptor membrane component 1). Immunocytochemistry reveals that both PGRMC1 and SW120, a fluorescent sigma-2 receptor ligand, colocalize with molecular markers of the endoplasmic reticulum and mitochondria in HeLa cells. Overexpression and knockdown of the PGRMC1 protein results in an increase and a decrease in binding of a sigma-2 selective radioligand, respectively. The identification of the putative sigma-2 receptor-binding site as PGRMC1 should stimulate the development of unique imaging agents and cancer therapeutics that target the sigma-2 receptor/PGRMC1 complex.
AB - The sigma-2 receptor, whose gene remains to be cloned, has been validated as a biomarker for tumour cell proliferation. Here we report the use of a novel photoaffinity probe, WC-21, to identify the sigma-2 receptor-binding site. WC-21, a sigma-2 ligand containing both a photoactive azide moiety and a fluorescein isothiocyanate group, irreversibly labels sigma-2 receptors in rat liver; the membrane-bound protein was identified as PGRMC1 (progesterone receptor membrane component 1). Immunocytochemistry reveals that both PGRMC1 and SW120, a fluorescent sigma-2 receptor ligand, colocalize with molecular markers of the endoplasmic reticulum and mitochondria in HeLa cells. Overexpression and knockdown of the PGRMC1 protein results in an increase and a decrease in binding of a sigma-2 selective radioligand, respectively. The identification of the putative sigma-2 receptor-binding site as PGRMC1 should stimulate the development of unique imaging agents and cancer therapeutics that target the sigma-2 receptor/PGRMC1 complex.
UR - http://www.scopus.com/inward/record.url?scp=79960099287&partnerID=8YFLogxK
U2 - 10.1038/ncomms1386
DO - 10.1038/ncomms1386
M3 - Article
C2 - 21730960
AN - SCOPUS:79960099287
VL - 2
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 380
ER -