G protein-coupled receptors: walking hand-in-hand, talking hand-in-hand?
Most cells express a panel of different G protein-coupled receptors (GPCRs) allowing them to respond to at least a corresponding variety of extracellular ligands. In order to come to an integrative well-balanced functional response these ligand-receptor pairs can often cross-regulate each other. Although most GPCRs are fully capable to induce intracellular signalling upon agonist binding on their own, many GPCRs, if not all, appear to exist and function in homomeric and/or heteromeric assemblies for at least some time. Such heteromeric organization offers unique allosteric control of receptor pharmacology and function between the protomers and might even unmask 'new' features. However, it is important to realize that some functional consequences that are proposed to originate from heteromeric receptor interactions may also be observed due to intracellular crosstalk between signalling pathways of non-associated GPCRs.
Leiden/Amsterdam Center for Drug Research (LACDR), Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
Henry F
HF
Vischer
Anne O
AO
Watts
Saskia
S
Nijmeijer
Rob
R
Leurs
D000494:Allosteric Regulation; D000818:Animals; D006801:Humans; D055503:Protein Multimerization; D020239:Receptor Cross-Talk; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction
D043562:Receptors, G-Protein-Coupled
Mol Pharmacol. 2005 Feb;67(2):460-9
15509716
Nat Chem Biol. 2009 Mar;5(3):131-4
19219011
Mol Pharmacol. 2005 Sep;68(3):568-78
15923381
Cell. 2003 Oct 31;115(3):255-66
14636554
Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):654-9
17194762
J Biol Chem. 2009 Nov 6;284(45):31270-9
19758998
J Physiol. 2009 Nov 15;587(Pt 22):5337-44
19723778
J Biol Chem. 2008 Sep 19;283(38):26016-25
18644790
Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1548-53
14757828
FEBS J. 2005 Jun;272(12):2947-55
15955055
Br J Pharmacol. 2008 Mar;153 Suppl 1:S379-88
18059321
Mol Pharmacol. 2000 Oct;58(4):677-83
10999936
J Pharmacol Exp Ther. 2005 Apr;313(1):16-23
15615865
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3684-9
10725388
EMBO J. 2009 Nov 4;28(21):3315-28
19763081
FEBS Lett. 2008 Sep 3;582(20):2979-84
18675812
Neuron. 2000 Jul;27(1):97-106
10939334
J Biol Chem. 2010 Sep 17;285(38):29632-41
20622011
Pharmacol Rev. 2007 Mar;59(1):5-13
17329545
FASEB J. 2007 Aug;21(10):2455-65
17384143
J Neurosci. 2000 Nov 15;20(22):RC110
11069979
Mol Pharmacol. 2009 Aug;76(2):264-74
19429716
Mol Pharmacol. 2006 May;69(5):1652-61
16467191
J Biol Chem. 2002 Nov 22;277(47):44925-31
12244098
Biochem J. 2008 Aug 15;414(1):121-31
18452403
Curr Opin Pharmacol. 2010 Feb;10(1):23-9
19850521
Anal Biochem. 2004 Jun 15;329(2):253-62
15158484
Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17495-500
16301531
Trends Neurosci. 2008 Feb;31(2):74-81
18199492
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3125-8
17360618
Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2693-8
20133736
Trends Pharmacol Sci. 2008 Oct;29(10):528-35
18760490
Nat Rev Cancer. 2007 Feb;7(2):79-94
17251915
EMBO J. 2001 May 1;20(9):2152-9
11331581
Mol Pharmacol. 2006 Jan;69(1):363-73
16244179
Mol Biol Cell. 2005 Dec;16(12):5572-8
16176975
Cell Signal. 2010 Apr;22(4):684-96
20043990
J Biol Chem. 2004 Feb 13;279(7):5152-61
14610092
Cell. 2008 Oct 31;135(3):561-71
18984166
J Biol Chem. 2008 Apr 25;283(17):11424-34
18319252
Pharmacol Ther. 2007 Sep;115(3):410-8
17655934
EMBO J. 2006 Jul 12;25(13):3012-23
16778767
J Neurosci. 2002 Sep 1;22(17):7352-61
12196556
Cell Signal. 2007 Sep;19(9):1928-38
17561373
J Biol Chem. 1996 Jan 19;271(3):1507-13
8576145
Nat Chem Biol. 2008 Feb;4(2):126-31
18193048
Am J Physiol Endocrinol Metab. 2008 Jan;294(1):E61-8
17971513
J Biol Chem. 2006 Dec 15;281(50):38812-24
17015451
Annu Rev Pharmacol Toxicol. 2007;47:53-87
17029567
Trends Pharmacol Sci. 2009 May;30(5):249-59
19375807
Pharmacol Ther. 2003 Jun;98(3):325-54
12782243
Science. 2005 Apr 22;308(5721):512-7
15845844
J Pharmacol Exp Ther. 2004 Oct;311(1):131-8
15159444
J Biol Chem. 1999 Sep 24;274(39):27642-50
10488104
Trends Biochem Sci. 2004 Nov;29(11):618-25
15501681
Nature. 1998 Dec 17;396(6712):683-7
9872317
J Biol Chem. 2005 Nov 18;280(46):38478-88
16159882
EMBO J. 2006 Dec 13;25(24):5693-702
17139258
J Biol Chem. 2008 Feb 15;283(7):4387-94
18033822
Br J Pharmacol. 2009 May;157(1):64-75
19413572
J Biol Chem. 2010 Feb 26;285(9):6337-47
20026606
Cell Signal. 2003 Jun;15(6):549-57
12681442
Trends Pharmacol Sci. 2009 Apr;30(4):182-7
19269046
Sci STKE. 2003 Jun 17;2003(187):RE9
12815191
Nat Rev Neurosci. 2001 Apr;2(4):274-86
11283750
Biochem Biophys Res Commun. 1975 Jun 16;64(4):1160-8
1137592
Nat Methods. 2008 Aug;5(8):727-33
18587404
J Biol Chem. 2004 Aug 20;279(34):35671-8
15159403
EMBO J. 2008 Sep 3;27(17):2293-304
18668123
Nat Rev Mol Cell Biol. 2008 Jan;9(1):60-71
18043707
J Biol Chem. 2003 Jun 27;278(26):23731-7
12690115
J Neurochem. 2010 Mar;112(6):1442-53
20050980
J Biol Chem. 2006 Mar 3;281(9):5416-25
16368694
Mol Pharmacol. 2006 Apr;69(4):1194-206
16415177
Hum Mol Genet. 2005 Oct 15;14(20):2991-3002
16135555
Trends Pharmacol Sci. 2010 Nov;31(11):499-508
20870299
Nat Chem Biol. 2009 Sep;5(9):688-95
19648932
J Biol Chem. 2002 May 3;277(18):15795-800
11859079
Mol Pharmacol. 2007 Apr;71(4):1015-29
17220353
Cell. 1995 Jan 27;80(2):213-23
7834741
Nature. 2008 Mar 6;452(7183):93-7
18297054
Nature. 1999 Jun 17;399(6737):697-700
10385123
Trends Endocrinol Metab. 2004 Jul;15(5):222-8
15223052
Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4903-8
12679517
Hum Mol Genet. 2006 Jul 15;15(14):2200-9
16740594
Mol Endocrinol. 2002 Jun;16(6):1299-308
12040016
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12199-204
17620610
FEBS J. 2005 Jun;272(12):2914-25
15955052
Br J Pharmacol. 2008 Mar;153 Suppl 1:S167-76
18193069
Biochim Biophys Acta. 2010 Dec;1803(12):1347-58
20831885
J Biol Chem. 2010 Aug 27;285(35):27346-27359
20562103
EMBO Rep. 2006 Nov;7(11):1094-8
17077864
Mol Pharmacol. 2006 Aug;70(2):686-96
16682504
Br J Pharmacol. 2009 Sep;158(1):5-14
19309353
Nat Chem Biol. 2010 Aug;6(8):587-94
20622858
J Biol Chem. 2004 Apr 9;279(15):15541-9
14736874
Biochemistry. 1998 Nov 10;37(45):15773-84
9843382
Biochem Biophys Res Commun. 2010 Mar 26;394(1):222-7
20197060
Nature. 1998 Dec 17;396(6712):674-9
9872315
Nat Cell Biol. 2006 Jun;8(6):571-80
16699502
Mol Endocrinol. 1997 Oct;11(11):1659-68
9328348
J Biol Chem. 2002 Feb 1;277(5):3236-41
11711539
Pharmacol Ther. 2004 Jul;103(1):21-80
15251227
Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10024-8
7937831
FEBS J. 2009 Feb;276(3):760-75
19143836
Nat Methods. 2009 Mar;6(3):225-30
19234451
J Mol Biol. 2010 Jun 11;399(3):501-11
20417217
Curr Opin Pharmacol. 2010 Feb;10(1):1-5
20015687
Biochem J. 2009 Jan 1;417(1):161-72
18764782
J Neurochem. 2009 Jun;109(5):1497-507
19344374
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):3103-7
8385357
J Biol Chem. 2005 Aug 5;280(31):28663-74
15946947
Nature. 1998 Dec 17;396(6712):679-82
9872316
Nature. 2005 Jan 20;433(7023):269-77
15662415
Biochem Pharmacol. 2007 Apr 15;73(8):1043-50
17011524
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3324-9
11880656
Mol Endocrinol. 2004 Apr;18(4):968-78
14726491
J Biol Chem. 1996 Jul 5;271(27):16384-92
8663163
J Biol Chem. 2007 May 18;282(20):14875-81
17395586
Science. 2003 Aug 8;301(5634):850-3
12869700
Cell. 2004 Oct 29;119(3):343-54
15507206
J Biol Chem. 2010 Jul 23;285(30):23318-30
20489201
J Biol Chem. 2009 Sep 25;284(39):26732-41
19542234
Nat Struct Mol Biol. 2004 Aug;11(8):706-13
15235591
J Biol Chem. 1996 Nov 8;271(45):28612-6
8910492
Nat Methods. 2008 Jun;5(6):561-7
18488035
J Biol Chem. 2007 Oct 12;282(41):30062-9
17715128
J Mol Biol. 2003 Jun 13;329(4):815-29
12787680
Mol Pharmacol. 2002 Aug;62(2):343-50
12130687
Mol Pharmacol. 2006 Nov;70(5):1783-91
16926282
Nat Rev Drug Discov. 2008 Apr;7(4):339-57
18382464
J Biol Chem. 2011 Jan 14;286(2):1420-8
20966068
Biochem J. 1999 Oct 1;343 Pt 1:231-9
10493934
EMBO J. 2009 Aug 5;28(15):2195-208
19590495
J Biol Chem. 2003 Jun 20;278(25):23085-93
12686555
Bioinformatics. 2010 Jul 15;26(14):1804-5
20501551
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2319-24
20080658
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7682-7
17452637
Mol Pharmacol. 2009 Jun;75(6):1296-9
19273553
Nat Rev Drug Discov. 2007 Jul;6(7):569-82
17599086
J Biol Chem. 2004 Aug 6;279(32):33390-7
15155738
J Neurosci. 2001 Feb 15;21(4):1189-202
11160389
Trends Biotechnol. 2010 Aug;28(8):407-15
20542584
Biochem Biophys Res Commun. 2008 Dec 5;377(1):93-7
18823943