Nina Wettschureck and Stefan Offermanns - Physiological Reviews

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1162 NINA WETTSCHURECK AND STEFAN OFFERMANNS TABLE 1—Continued Endogenous Ligand(s) Receptor Coupling to G Protein Subclass(es) Reference Nos. Amylin Angiotensin II Apelin Bradykinin Calcitonin Calcitonin gene-related peptide (CGRP) CC chemokines CXC chemokines CX3C chemokines Cholecyctokinin (CCK-8) Complement C3a/C5a Corticitropin-releasing factor (CRF), urocortin AMY1 (CT�RAMP1), AMY2 (CT�RAMP2), AMY3 (CT�RAMP3) AT1 AT2 APJ B1,B2 CT CGRP1 (CL�RAMP1) CCR1,2,3,4,5,6,7,8,9,10 CXCR1,2,3,4,5,6 XCL1, XCL2, CX3L1 CCK1, CCK2 C3a, C5a CRF1, CRF2 Gs Gq/11, G12/13, Gi/o ? Gi/o Gq/11 Gs,Gq/11 Gs,Gq/11 Gi/o Gi/o Gi/o Gq/11, Gs Gi/o Gs 525 134 627 378 525 525 466, 467 466, 467 466, 467 582 208 239 Endothelin-1, -2, -3 Follicle-stimulating hormone (FSH) Formyl-Met-Leu-Phe (fMLP) Galanin, galanin-like peptide Gastric inhibitory peptide Gastrin Gastrin-releasing peptide (GRP), bombesin ETA (ET-1, ET-2), ETB (ET-1, -2, -3) FSH FPR GAL1, GAL3 GAL2 GIP CCK2 BB2 Gq/11, G12/13, Gs Gs Gi/o Gi/o Gi/o, Gq/11, G12/13 Gs Gq/11 Gq/11 131 648 373 657 657 332, 431 582 36 Ghrelin Glucagon Glucagon-like peptide Gonadotropin-releasing hormone Growth hormone-releasing hormone Kisspeptins, metastin Luteinizing hormone, choriogonadotropin GHS-R Glucagon GLP1, GLP2 GnRH GHRH GPR54 LSH Gq/11 Gs Gs Gq/11 Gs Gq/11 Gs,Gi 342 431 431 445 206, 431 137, 575 648 Melanin-concentrating hormone Melanocortins Motilin Neurokinin-A/-B (NK-A/-B) Neuromedin-B, bombesin Neuromedin U Neuropeptide FF & AF Neuropeptide W-23, W-30 Neuropeptide Y (NPY) etc. Neurotensin Opioids (�-endorphin, Met/Leuenkephalin, dynorphin A, nociceptin/ orphanin FQ) MCH1 MCH2 MC1,MC3,MC4,MC5 GPR38 NK2 (NK-A), NK3 (NK-B) BB1 NMU1 (FM-3), NMU2 (FM-4) NPFF1, NPFF2 GRP7, GPR8 Y1,Y2,Y4,Y5,Y6 NTS1, NTS2 �, �, �, ORL1 Gi/o? Gq/11 Gs Gq/11 Gq/11 Gq/11 Gq/11 Gi/o Gi/o Gi/o Gq/11 Gi/o 63 682 173 513 496 67 54 580 440 654 370 Orexin A/B Oxytocin Parathyroid hormone (related peptide) Prokineticin-1,2 Prolactin-releasing peptide Relaxin, insulin-like 3 Secretin Somatostatin Substance P (SP) Thyrotropin (TSH) Thyrotropin-releasing hormone (TRH) Urotensin II Vasoactive intestinal polypeptide (VIP), PACAP OX1, OX2 OT PTH/PTHrP PK-R1, PK-R2 PrRP (GPR10) LGR7, LGR8 Secretin SST1, SST2, SST3, SST4, SST5 NK1 TSH TRH-1, TRH-2 UT-II (GPR14) VPAC1, VPAC2, PAC1 Gs,Gq/11 Gq/11, Gi/o Gs,Gq/11 Gq/11 Gq/11 Gs Gs Gi/o Gq/11 Gs,Gq/11, Gi,G12/13 Gq/11 Gq/11 Gs 442 256 203 591 613 35 431 511 513 648 614 150 651 Vasopressin Proteases (the new NH2-terminal domain produced by proteolytic cleavage serves as a tethered ligand) V1a, V1b V2 Gq/11 Gs 256 256 Thrombin and others Trypsin and others PAR-1, PAR-3, PAR-4 PAR-2 Gq/11, G12/13, Gi/o Gq/11 271 271 Physiol Rev • VOL 85 • OCTOBER 2005 • www.prv.org
TABLE 1—Continued Sensory Stimuli Receptor The interaction of G proteins with the inner side of the plasma membrane is facilitated by lipid modifications of both the �-subunit as well as of the �-subunit of the ��-complex (97, 448, 589, 728). Recent data provide evidence that heterotrimeric G proteins of the G i family are also involved in receptor-independent processes (52, 413), which appear to be critically involved in the positioning of the mitotic spindle and the attachment of microtubules to the cell cortex (234). These processes also involve a group of proteins that carry a so-called GoLoco motif which functions as a guanine nucleotide dissociation inhibitor (684). B. G Protein �-Subunits and ��-Complexes The functional versatility of the G protein-mediated signaling system is based on its modular architecture and on the fact that there are numerous subtypes of G proteins. The �-subunits that define the basic properties of a heterotrimeric G protein can be divided into four families, G� s,G� i/G� o,G� q/G� 11, and G� 12/G� 13 (Table 2). Each family consists of various members that often show very specific expression patterns. Members of one family are structurally similar and often share some of their functional properties. The ��-complex of mammalian G proteins is assembled from a repertoire of 5 G protein �-subunits and 12 �-subunits (Table 2). While �1- to �4-subunits form a tight complex with �-subunits which can only be separated under denaturing conditions, the �5-subunit interaction with �-subunits is comparably weak (347, 543). The �5-subunit is an exception in that it can also be found in a complex with a subgroup of RGS proteins (689). The ��-complex was initially regarded as a more CELLULAR FUNCTIONS OF G PROTEINS 1163 Coupling to G Protein Subclass(es) Reference Nos. Light �500 nm (max. absorption) �426 nm (max. absorption) �530 nm (max. absorption) �560 nm (max. absorption) �425–480 nm (max. absorption) Taste Rhodopsin (11-cis-retinal) Blue-opsin (11-cis-retinal) Green-opsin (11-cis-retinal) Red-opsin (11-cis-retinal) Melanopsin (11-cis-retinal) Gt-r Gt-c Gt-c Gt-c Gq/11? 717 471 471 471 436, 505, 530 Umami Sweet Bitter T1R1 � T1R3 mGluR4 T1R2 � T1R3 T2 receptor group (many; �25 in human, �36 in mouse) Ggust? Gi/o Ggust? Ggust? 457, 477, 730 95 457, 477, 730 94, 457, 463 Odorants many (�350 in human, �1,000 in mouse) Golf 77, 457 Pheromones V1 group (few in human, �150 in Gi2 ? 428, 457 mouse) V2 group (none in human, �150 in mouse) In the reference column, reviews are cited whenever possible to limit the number of references. Physiol Rev • VOL 85 • OCTOBER 2005 • www.prv.org G o ? 428, 457 passive partner of the G protein �-subunit. However, it has become clear that ��-complexes freed from the G protein �-subunit can regulate various effectors (112). These ��-mediated signaling events include the regulation of ion channels (488), of particular isoforms of adenylyl cyclase and phospholipase C (169, 615), as well as of phosphoinositide-3-kinase isoforms (641). With a few exceptions, the ability of different ��-combinations to regulate effector functions does not dramatically differ (112). Most receptors are able to activate more than one G protein subtype. The activation of a G protein-coupled receptor therefore usually results in the activation of several signal transduction cascades via G protein �-subunits as well as through the freed ��-complex. The pattern of G proteins activated by a given receptor determines the cellular and biological response, and activated receptors that lead to functionally similar or identical cellular effects usually activate the same G protein subtypes. The G protein receptor interaction in general does not occur in an absolutely specific or in a completely promiscuous manner. Some receptors appear to interact only with certain G protein subforms, and in some cellular systems, the compositions of defined G protein-mediated signaling pathways can be very specific. However, there are some characteristic patterns of receptor-G protein coupling that have been described for the majority of receptors (Fig. 2). The G proteins of the G i/G o family are widely expressed and especially the �-subunits of G i1, G i2 and G i3 have been shown to mediate receptor-dependent inhibition of various types of adenylyl cyclases (615). Because the expression levels of G i and G o are relatively
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Page 3: TABLE 1. Physiological ligands of G
Page 7 and 8: FIG. 1. Functional cycle of G prote
Page 9 and 10: promoter driving the expression of
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Page 23 and 24: A. Visual System The human retina c
Page 25 and 26: addressed the role of G proteins in
Page 27 and 28: C. G i-Mediated Cell Transformation
Page 29 and 30: 45. Berstein G, Blank JL, Jhon DY,
Page 31 and 32: 123. Cyster JG. Chemokines, sphingo
Page 33 and 34: 207. Gehrmann J, Meister M, Maguire
Page 35 and 36: 290. Imamura T, Vollenweider P, Ega
Page 37 and 38: 369. Laurent E, Mockel J, Van Sande
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Page 41 and 42: 533. Radu CG, Yang LV, Riedinger M,
Page 43 and 44: 616. Suwazono Y, Okubo Y, Kobayashi
Page 45 and 46: 695. Wu D, Huang CK, and Jiang H. R

Nina Wettschureck and Stefan Offermanns - Physiological Reviews

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