GPCRs regulate the assembly of a multienzyme complex for purine biosynthesis

Florence Verrier, Songon An, Ann M. Ferrie, Haiyan Sun, Minjoung Kyoung, Huayun Deng, Ye Fang, Stephen J. Benkovic

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)909-915
Number of pages7
JournalNature Chemical Biology
Volume7
Issue number12
DOIs
StatePublished - Dec 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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