TY - JOUR
T1 - GPCRs regulate the assembly of a multienzyme complex for purine biosynthesis
AU - Verrier, Florence
AU - An, Songon
AU - Ferrie, Ann M.
AU - Sun, Haiyan
AU - Kyoung, Minjoung
AU - Deng, Huayun
AU - Fang, Ye
AU - Benkovic, Stephen J.
N1 - Funding Information:
This work was funded by US National Institutes of Health grant GM24129 (S.J.B.).
PY - 2011/12
Y1 - 2011/12
N2 - G proteinĝ€"coupled receptors (GPCRs) transmit exogenous signals to the nucleus, promoting a myriad of biological responses via multiple signaling pathways in both healthy and cancerous cells. However, little is known about the response of cytosolic metabolic pathways to GPCR-mediated signaling. Here we applied fluorescent live-cell imaging and label-free dynamic mass redistribution assays to study whether purine metabolism is associated with GPCR signaling. Through a library screen of GPCR ligands in conjunction with live-cell imaging of a metabolic multienzyme complex for de novo purine biosynthesis, the purinosome, we demonstrated that the activation of endogenous G ± i-coupled receptors correlates with purinosome assembly and disassembly in native HeLa cells. Given the implications of GPCRs in mitogenic signaling and of the purinosome in controlling metabolic flux via de novo purine biosynthesis, we hypothesize that regulation of purinosome assembly and disassembly may be one of the downstream events of mitogenic GPCR signaling in human cancer cells.
AB - G proteinĝ€"coupled receptors (GPCRs) transmit exogenous signals to the nucleus, promoting a myriad of biological responses via multiple signaling pathways in both healthy and cancerous cells. However, little is known about the response of cytosolic metabolic pathways to GPCR-mediated signaling. Here we applied fluorescent live-cell imaging and label-free dynamic mass redistribution assays to study whether purine metabolism is associated with GPCR signaling. Through a library screen of GPCR ligands in conjunction with live-cell imaging of a metabolic multienzyme complex for de novo purine biosynthesis, the purinosome, we demonstrated that the activation of endogenous G ± i-coupled receptors correlates with purinosome assembly and disassembly in native HeLa cells. Given the implications of GPCRs in mitogenic signaling and of the purinosome in controlling metabolic flux via de novo purine biosynthesis, we hypothesize that regulation of purinosome assembly and disassembly may be one of the downstream events of mitogenic GPCR signaling in human cancer cells.
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U2 - 10.1038/nchembio.690
DO - 10.1038/nchembio.690
M3 - Article
C2 - 22020552
AN - SCOPUS:81355148507
SN - 1552-4450
VL - 7
SP - 909
EP - 915
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 12
ER -