{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:05:25Z","timestamp":1773248725930,"version":"3.50.1"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2008,9,26]],"date-time":"2008-09-26T00:00:00Z","timestamp":1222387200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1000185","type":"journal-article","created":{"date-parts":[[2008,9,25]],"date-time":"2008-09-25T22:13:02Z","timestamp":1222380782000},"page":"e1000185","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":38,"title":["A Dual Receptor Crosstalk Model of G-Protein-Coupled Signal Transduction"],"prefix":"10.1371","volume":"4","author":[{"given":"Patrick","family":"Flaherty","sequence":"first","affiliation":[]},{"given":"Mala L.","family":"Radhakrishnan","sequence":"additional","affiliation":[]},{"given":"Tuan","family":"Dinh","sequence":"additional","affiliation":[]},{"given":"Robert A.","family":"Rebres","sequence":"additional","affiliation":[]},{"given":"Tamara I.","family":"Roach","sequence":"additional","affiliation":[]},{"given":"Michael I.","family":"Jordan","sequence":"additional","affiliation":[]},{"given":"Adam P.","family":"Arkin","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2008,9,26]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.1242\/jcs.00902","article-title":"G-protein-coupled receptors at a glance.","volume":"116","author":"WK Kroeze","year":"2003","journal-title":"J Cell Sci"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj20030312","article-title":"Mechanisms of cross-talk between G-protein-coupled receptors resulting in enhanced release of intracellular Ca<sup>2+<\/sup>.","volume":"374","author":"TD Werry","year":"2003","journal-title":"Biochem J"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1016\/S0021-9258(18)69103-3","article-title":"G protein involvement in receptor-effector coupling.","volume":"263","author":"PJ Casey","year":"1988","journal-title":"J Biol Chem"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"5297","DOI":"10.1073\/pnas.90.11.5297","article-title":"Activation of phospholipase C \u03b2<sub>2<\/sub> by the \u03b1 and \u03b2\u03b3 subunits of trimeric GTP-binding protein.","volume":"90","author":"D Wu","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"9539","DOI":"10.1073\/pnas.96.17.9539","article-title":"Rapid GTP binding and hydrolysis by G<sub>q<\/sub> promoted by receptor and GTPase-activating proteins.","volume":"96","author":"S Mukhopadhyay","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1146\/annurev.biochem.73.071403.161303","article-title":"Inositol 1,4,5-trisphosphate receptors as signal integrators.","volume":"73","author":"RL Patterson","year":"2004","journal-title":"Annu Rev Biochem"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"46886","DOI":"10.1074\/jbc.M307853200","article-title":"Activation mechanisms of conventional protein kinase C isoforms are determined by the ligand affinity and conformational flexibility of their C1 domains.","volume":"278","author":"B Ananthanarayanan","year":"2003","journal-title":"J Biol Chem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0898-6568(03)00099-8","article-title":"Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases.","volume":"15","author":"P Penela","year":"2003","journal-title":"Cell Signal"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"11707","DOI":"10.1074\/jbc.270.20.11707","article-title":"Pleckstrin homology domain-mediated membrane association and activation of the \u03b2-adrenergic receptor kinase requires coordinate interaction with G<sub>\u03b2\u03b3<\/sub> subunits and lipid.","volume":"270","author":"JA Pitcher","year":"1995","journal-title":"J Biol Chem"},{"key":"ref10","article-title":"Biochemistry. 5th ed","author":"JM Berg","year":"2002"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2174\/0929867053363379","article-title":"Targeting C5a: recent advances in drug discovery.","volume":"12","author":"M Allegretti","year":"2005","journal-title":"Curr Med Chem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"26051","DOI":"10.1074\/jbc.M102568200","article-title":"P2Y<sub>6<\/sub> nucleotide receptor mediates monocyte interleukin-8 production in response to UDP or lipopolysaccharide.","volume":"276","author":"M Warny","year":"2001","journal-title":"J Biol Chem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"7617","DOI":"10.1073\/pnas.121587098","article-title":"Heteromeric association creates a P2Y-like adenosine receptor.","volume":"98","author":"K Yoshioka","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1529\/biophysj.103.035253","article-title":"A signal transduction pathway model prototype I: from agonist to cellular endpoint.","volume":"87","author":"TJ Lukas","year":"2004","journal-title":"Biophys J"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/S0006-3495(02)73901-5","article-title":"Simulations of inositol phosphate metabolism and its interaction with InsP<sub>3<\/sub>-mediated calcium release.","volume":"83","author":"J Mishra","year":"2002","journal-title":"Biophys J"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0022-5193(03)00079-1","article-title":"Metabotropic receptor activation, desensitization and sequestration\u2014I: modelling calcium and inositol 1,4,5-trisphosphate dynamics following receptor activation.","volume":"223","author":"G Lemon","year":"2003","journal-title":"J Theor Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1529\/biophysj.106.097501","article-title":"A kinetic model for calcium dynamics in RAW 264.7 cells: 2. Knockdown response and long-term response.","volume":"93","author":"MR Maurya","year":"2007","journal-title":"Biophys J"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1529\/biophysj.106.097469","article-title":"A kinetic model for calcium dynamics in RAW 264.7 Cells: 1. Mechanisms, parameters and sub-populational variability.","volume":"93","author":"MR Maurya","year":"2007","journal-title":"Biophys J"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"10626","DOI":"10.1073\/pnas.96.19.10626","article-title":"Crosstalk between G\u03b1<sub>i<\/sub>- and G\u03b1<sub>q<\/sub>-coupled receptors is mediated by G\u03b2\u03b3 exchange.","volume":"96","author":"U Quitterer","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1073\/pnas.93.7.2827","article-title":"G protein subunits and the stimulation of phospholipase C by G<sub>s<\/sub>- and G<sub>i<\/sub>-coupled receptors: lack of receptor selectivity of G\u03b1<sub>16<\/sub> and evidence for a synergic interaction between G\u03b2\u03b3 and the \u03b1 subunit of a receptor activated G protein.","volume":"93","author":"X Zhu","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1074-7613(00)80453-7","article-title":"Heterotrimeric G protein signaling: roles in immune function and fine-tuning by RGS proteins.","volume":"8","author":"JH Kehrl","year":"1998","journal-title":"Immunity"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1146\/annurev.biochem.69.1.795","article-title":"GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins.","volume":"69","author":"EM Ross","year":"2000","journal-title":"Annu Rev Biochem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"5438","DOI":"10.1074\/jbc.M007699200","article-title":"Protein kinase C phosphorylates RGS2 and modulates its capacity for negative regulation of G\u03b1<sub>11<\/sub> signaling.","volume":"276","author":"ML Cunningham","year":"2001","journal-title":"J Biol Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/S1357-2725(01)00141-8","article-title":"RGS2: a multifunctional regulator of G-protein signaling.","volume":"34","author":"JH Kehrl","year":"2002","journal-title":"Int J Biochem Cell Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0006-3495(92)81870-2","article-title":"Two roles of Ca<sup>2+<\/sup> in agonist stimulated Ca<sup>2+<\/sup> oscillations.","volume":"61","author":"J Keizer","year":"1992","journal-title":"Biophys J"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1126\/science.2452482","article-title":"Highly cooperative opening of calcium channels by inositol 1,4,5-trisphosphate.","volume":"240","author":"T Meyer","year":"1988","journal-title":"Science"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"5051","DOI":"10.1073\/pnas.85.14.5051","article-title":"Molecular model for receptor-stimulated calcium spiking.","volume":"85","author":"T Meyer","year":"1988","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"13430","DOI":"10.1074\/jbc.271.23.13430","article-title":"Pertussis toxin-sensitive activation of phospholipase C by the C5a and fMet-Leu-Phe receptors.","volume":"271","author":"H Jiang","year":"1996","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1016\/S0021-9258(18)53431-1","article-title":"Activation of phospholipase C isozymes by G protein \u03b2\u03b3 subunits.","volume":"268","author":"D Park","year":"1993","journal-title":"J Biol Chem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"9667","DOI":"10.1016\/S0021-9258(18)98401-2","article-title":"Regulation of purified subtypes of phosphatidylinositol-specific phospholipase C \u03b2 by G protein \u03b1 and \u03b2\u03b3 subunits.","volume":"268","author":"AV Smrcka","year":"1993","journal-title":"J Biol Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"25335","DOI":"10.1016\/S0021-9258(18)47252-3","article-title":"Regulation of phospholipase C-\u03b24 by ribonucleotides and the \u03b1 subunit of G<sub>q<\/sub>.","volume":"269","author":"CW Lee","year":"1994","journal-title":"J Biol Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"7593","DOI":"10.1016\/S0021-9258(17)37328-3","article-title":"Activation of phospholipase C \u03b24 by heterotrimeric GTP-binding proteins.","volume":"269","author":"H Jiang","year":"1994","journal-title":"J Biol Chem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1021\/bi9821519","article-title":"Determination of the affinities between heterotrimeric G protein subunits and their phospholipase C-\u03b2 effectors.","volume":"38","author":"LW Runnels","year":"1999","journal-title":"Biochemistry"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1146\/annurev.biochem.70.1.281","article-title":"Regulation of phosphoinositide-specific phospholipase C.","volume":"70","author":"SG Rhee","year":"2001","journal-title":"Annu Rev Biochem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"30220","DOI":"10.1074\/jbc.M004276200","article-title":"Molecular mechanism of the inhibition of phospholipase C \u03b2<sub>3<\/sub> by protein kinase C.","volume":"275","author":"C Yue","year":"2000","journal-title":"J Biol Chem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/15216540215673","article-title":"Novel mechanisms for feedback regulation of phospholipase C-\u03b2 activity.","volume":"54","author":"I Litosch","year":"2002","journal-title":"IUBMB Life"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni1097","article-title":"Protein kinase C and beyond.","volume":"5","author":"M Spitaler","year":"2004","journal-title":"Nat Immunol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1002\/(SICI)1521-4141(199909)29:09<3035::AID-IMMU3035>3.0.CO;2-Z","article-title":"Ligand-induced phosphorylation of anaphylatoxin receptors C3aR and C5aR is mediated by G protein-coupled receptor kinases.","volume":"29","author":"P Langkabel","year":"1999","journal-title":"Eur J Immunol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"13759","DOI":"10.1073\/pnas.0606179103","article-title":"A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression.","volume":"103","author":"KJ Shin","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/ncb1418","article-title":"A global analysis of cross-talk in a mammalian cellular signalling network.","volume":"8","author":"M Natarajan","year":"2006","journal-title":"Nat Cell Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"9895","DOI":"10.1073\/pnas.89.20.9895","article-title":"A single-pool inositol 1,4,5-trisphosphate-receptor-based model for agonist-stimulated oscillations in Ca<sup>2+<\/sup> concentration.","volume":"89","author":"GW De Young","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1145\/1089014.1089020","article-title":"SUNDIALS: Suite of Nonlinear and Differential\/Algebraic Equation Solvers.","volume":"31","author":"AC Hindmarsh","year":"2005","journal-title":"ACM Trans Math Softw"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0091-679X(08)60978-4","article-title":"Fluorescent indicators of ion concentrations.","volume":"30","author":"RY Tsien","year":"1989","journal-title":"Methods Cell Biol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of Ca<sup>2+<\/sup> indicators with greatly improved fluorescence properties.","volume":"260","author":"G Grynkiewicz","year":"1985","journal-title":"J Biol Chem"},{"key":"ref45","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-4145-2","article-title":"Monte Carlo Statistical Methods","author":"CP Robert","year":"2004"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1214\/ss\/1177011136","article-title":"Inference from iterative simulation using multiple sequences.","volume":"7","author":"A Gelman","year":"1992","journal-title":"Stat Sci"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000185","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T04:11:59Z","timestamp":1631851919000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000185"}},"subtitle":[],"editor":[{"given":"Anand","family":"Asthagiri","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2008,9,26]]},"references-count":46,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2008,9,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000185","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9,26]]}}}