Seven-transmembrane receptors (original) (raw)

• Lefkowitz, R. J. The superfamily of heptahelical receptors. Nature Cell Biol. 2, E133–E136 (2000).A historical perspective describing the origins of the field of 7TM receptor signalling in the 1970s and 1980s.
  CAS PubMed Google Scholar
• Dixon, R. A. et al. Cloning of the gene and cDNA for mammalian β-adrenergic receptor and homology with rhodopsin. Nature 321, 75–79 (1986).This paper reports the cloning of the β2-adrenergic receptor, its analogy and 7TM homology with rhodopsin, and speculates on the existence of a large family of such receptors.
  CAS PubMed Google Scholar
• Dohlman, H. G., Thorner, J., Caron, M. G. & Lefkowitz, R. J. Model systems for the study of seven-transmembrane-segment receptors. Annu. Rev. Biochem. 60, 653–688 (1991).
  CAS PubMed Google Scholar
• Lee, D. K., George, S. R. & O'Dowd, B. F. Novel G-protein-coupled receptor genes expressed in the brain: continued discovery of important therapeutic targets. Expert Opin. Ther. Targets 6, 1–18 (2002).
  Google Scholar
• Palczewski, K. et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289, 739–745 (2000).Describes the crystal structure of the only 7TM receptor so far solved.
  CAS PubMed Google Scholar
• Rodbell, M., Birnbaumer, L., Pohl, S. L. & Krans, H. M. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. V. An obligatory role of guanylnucleotides in glucagon action. J. Biol. Chem. 246, 1877–1882 (1971).
  CAS PubMed Google Scholar
• Gilman, A. G. G proteins: transducers of receptor-generated signals. Annu. Rev. Biochem. 56, 615–649 (1987).
  CAS PubMed Google Scholar
• Ballesteros, J. A. et al. Activation of the β2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J. Biol. Chem. 276, 29171–29177 (2001).
  CAS PubMed Google Scholar
• Farahbakhsh, Z. T., Ridge, K. D., Khorana, H. G. & Hubbell, W. L. Mapping light-dependent structural changes in the cytoplasmic loop connecting helices C and D in rhodopsin: a site-directed spin labeling study. Biochemistry 34, 8812–8819 (1995).
  CAS PubMed Google Scholar
• De Vries, L. et al. The regulator of G protein signaling family. Annu. Rev. Pharmacol. Toxicol. 40, 235–271 (2000).
  CAS PubMed Google Scholar
• Ross, E. M. & Wilkie, T. M. GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu. Rev. Biochem. 69, 795–827 (2000).
  CAS PubMed Google Scholar
• Klein, S., Reuveni, H. & Levitzki, A. Signal transduction by a nondissociable heterotrimeric yeast G protein. Proc. Natl Acad. Sci. USA 97, 3219–3123 (2000).
  CAS PubMed PubMed Central Google Scholar
• Ferguson, S. S. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol. Rev. 53, 1–24 (2001).
  CAS PubMed Google Scholar
• Pitcher, J. A., Freedman, N. J. & Lefkowitz, R. J. G protein-coupled receptor kinases. Annu. Rev. Biochem. 67, 653–692 (1998).An extensive review of the biochemistry and regulation of the G-protein-coupled-receptor kinases.
  CAS PubMed Google Scholar
• Daaka, Y., Luttrell, L. M. & Lefkowitz, R. J. Switching of the coupling of the β2-adrenergic receptor to different G proteins by protein kinase A. Nature 390, 88–91 (1997).Describes a novel mechanism by which the G-protein coupling specificity of 7TM receptors might be regulated by protein-kinase-A-mediated receptor phosphorylation.
  CAS PubMed Google Scholar
• Zamah, A. M., Delahunty, M., Luttrell, L. M. & Lefkowitz, R. J. PKA-mediated phosphorylation of the β2-adrenergic receptor regulates its coupling to Gs and Gi: Demonstration in a reconstituted system. J. Biol. Chem. (in the press).
• Lawler, O. A., Miggin, S. M. & Kinsella, B. T. Protein kinase A-mediated phosphorylation of serine 357 of the mouse prostacyclin receptor regulates its coupling to Gs-, to Gi-, and to Gq-coupled effector signaling. J. Biol. Chem. 276, 33596–33607 (2001).
  CAS PubMed Google Scholar
• Krupnick, J. G. & Benovic, J. L. The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu. Rev. Pharmacol. Toxicol. 38, 289–319 (1998).An extensive review of this universal receptor regulatory system.
  CAS PubMed Google Scholar
• Zhang, J. et al. Molecular mechanisms of G protein-coupled receptor signaling: role of G protein-coupled receptor kinases and arrestins in receptor desensitization and resensitization. Receptors Channels 5, 193–199 (1997).
  CAS PubMed Google Scholar
• Winstel, R. et al. Protein kinase cross-talk: membrane targeting of the β-adrenergic receptor kinase by protein kinase C. Proc. Natl Acad. Sci. USA 93, 2105–2109 (1996).
  CAS PubMed PubMed Central Google Scholar
• Cong, M. et al. Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79. J. Biol. Chem. 276, 15192–15199 (2001).
  CAS PubMed Google Scholar
• Krueger, K. M., Daaka, Y., Pitcher, J. A. & Lefkowitz, R. J. The role of sequestration in G protein-coupled receptor resensitization. Regulation of β2-adrenergic receptor dephosphorylation by vesicular acidification. J. Biol. Chem. 272, 5–8 (1997).
  CAS PubMed Google Scholar
• Pitcher, J. A. et al. The G-protein-coupled receptor phosphatase: a protein phosphatase type 2A with a distinct subcellular distribution and substrate specificity. Proc. Natl Acad. Sci. USA 92, 8343–8347 (1995).
  CAS PubMed PubMed Central Google Scholar
• Tsao, P. & von Zastrow, M. Downregulation of G protein-coupled receptors. Curr. Opin. Neurobiol. 10, 365–369 (2000).
  CAS PubMed Google Scholar
• Collins, S., Caron, M. G. & Lefkowitz, R. J. Regulation of adrenergic receptor responsiveness through modulation of receptor gene expression. Annu. Rev. Physiol. 53, 497–508 (1991).
  CAS PubMed Google Scholar
• Lyubarsky, A. L. et al. RGS9-1 is required for normal inactivation of mouse cone phototransduction. Mol. Vis. 7, 71–78 (2001).
  CAS PubMed Google Scholar
• Oliveira-Dos-Santos, A. J. et al. Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc. Natl Acad. Sci. USA 97, 12272–12277 (2000).
  CAS PubMed PubMed Central Google Scholar
• Howard, A. D. et al. Orphan G-protein-coupled receptors and natural ligand discovery. Trends Pharmacol. Sci. 22, 132–140 (2001).
  CAS PubMed Google Scholar
• Kobilka, B. K. et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature 329, 75–79 (1987).
  CAS PubMed Google Scholar
• Fargin, A. et al. The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature 335, 358–360 (1988).
  CAS PubMed Google Scholar
• Hsu, S. Y. et al. Activation of orphan receptors by the hormone relaxin. Science 295, 671–674 (2002).
  CAS PubMed Google Scholar
• Lembo, P. M. et al. Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nature Neurosci. 5, 201–209 (2002).
  CAS PubMed Google Scholar
• Chuang, D. M. & Costa, E. Evidence for internalization of the recognition site of β-adrenergic receptors during receptor subsensitivity induced by (−)-isoproterenol. Proc. Natl Acad. Sci. USA 76, 3024–3028 (1979).
  CAS PubMed PubMed Central Google Scholar
• Chuang, D. M. & Costa, E. β-Adrenergic receptors of frog erythrocytes. Biochemical sequelae following stimulation with isoproterenol. Neurochem. Res. 4, 777–793 (1979).
  CAS PubMed Google Scholar
• Daaka, Y. et al. Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase. J. Biol. Chem. 273, 685–688 (1998).
  CAS PubMed Google Scholar
• Claing, A., Laporte, S. A., Caron, M. G. & Lefkowitz, R. J. Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and β-arrestin proteins. Prog. Neurobiol. 66, 61–79 (2002).Reviews the complex mechanisms involved in 7TM-receptor endocytosis.
  CAS PubMed Google Scholar
• Claing, A. et al. Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Proc. Natl Acad. Sci. USA 97, 1119–1124 (2000).
  CAS PubMed PubMed Central Google Scholar
• Smart, E. J. et al. Caveolins, liquid-ordered domains, and signal transduction. Mol. Cell. Biol. 19, 7289–7304 (1999).
  CAS PubMed PubMed Central Google Scholar
• Lohse, M. J. et al. β-Arrestin: a protein that regulates β-adrenergic receptor function. Science 248, 1547–1550 (1990).
  CAS PubMed Google Scholar
• Goodman, O. B., Jr et al. β-Arrestin acts as a clathrin adaptor in endocytosis of the β2-adrenergic receptor. Nature 383, 447–450 (1996).
  CAS PubMed Google Scholar
• Laporte, S. A. et al. The β-adrenergic receptor/β-arrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Proc. Natl Acad. Sci. USA 96, 3712–3717 (1999).
  CAS PubMed PubMed Central Google Scholar
• Gaidarov, I. et al. Arrestin function in G protein-coupled receptor endocytosis requires phosphoinositide binding. EMBO J. 18, 871–881 (1999).
  CAS PubMed PubMed Central Google Scholar
• Scott, M. G., Benmerah, A., Muntaner, O. & Marullo, S. Recruitment of activated G protein-coupled receptors to pre-existing clathrin-coated pits in living cells. J. Biol. Chem. 277, 3552–3559 (2002).
  CAS PubMed Google Scholar
• Santini, F., Gaidarov, I. & Keen, J. H. G protein-coupled receptor/arrestin3 modulation of the endocytic machinery. J. Cell Biol. 156, 665–676 (2002).
  CAS PubMed PubMed Central Google Scholar
• Oakley, R. H. et al. Differential affinities of visual arrestin, β-arrestin1, and β-arrestin2 for GPCRs delineate two major classes of receptors. J. Biol. Chem. 275, 17201–17210 (2000).
  CAS PubMed Google Scholar
• Luttrell, L. M. et al. β-Arrestin-dependent formation of β2 adrenergic receptor–Src protein kinase complexes. Science 283, 655–661 (1999).
  CAS PubMed Google Scholar
• Ahn, S. et al. Src-mediated tyrosine phosphorylation of dynamin is required for β2-adrenergic receptor internalization and mitogen-activated protein kinase signaling. J. Biol. Chem. 274, 1185–1188 (1999).
  CAS PubMed Google Scholar
• Ahn, S. et al. c-Src dependent tyrosine phosphorylation regulates dynamin self-assembly and receptor-mediated endocytosis. J. Biol. Chem. 277, 26642–26651 (2002).
  CAS PubMed Google Scholar
• Shenoy, S. K., McDonald, P. H., Kohout, T. A. & Lefkowitz, R. J. Regulation of receptor fate by ubiquitination of activated β2-adrenergic receptor and β-arrestin. Science 294, 1307–1313 (2001).
  CAS PubMed Google Scholar
• Pickart, C. M. Mechanisms underlying ubiquitination. Annu. Rev. Biochem. 70, 503–533 (2001).
  CAS PubMed Google Scholar
• McDonald, P. H. et al. Identification of NSF as a β-arrestin1-binding protein. Implications for β2-adrenergic receptor regulation. J. Biol. Chem. 274, 10677–10680 (1999).
  CAS PubMed Google Scholar
• Claing, A. et al. β-Arrestin-mediated ADP-ribosylation factor 6 activation and β2-adrenergic receptor endocytosis. J. Biol. Chem. 276, 42509–42513 (2001).
  CAS PubMed Google Scholar
• Premont, R. T. et al. β2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein. Proc. Natl Acad. Sci. USA 95, 14082–14087 (1998).
  CAS PubMed PubMed Central Google Scholar
• Cong, M. et al. Binding of the β2 adrenergic receptor to _N_-ethylmaleimide-sensitive factor regulates receptor recycling. J. Biol. Chem. 276, 45145–45152 (2001).
  CAS PubMed Google Scholar
• Seachrist, J. L. et al. Rab5 association with the angiotensin II type 1A receptor promotes Rab5 GTP binding and vesicular fusion. J. Biol. Chem. 277, 679–685 (2002).
  CAS PubMed Google Scholar
• Kohout, T. A. et al. β-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc. Natl Acad. Sci. USA 98, 1601–1606 (2001).
  CAS PubMed PubMed Central Google Scholar
• Marchese, A. & Benovic, J. L. Agonist-promoted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting. J. Biol. Chem. 276, 45509–45512 (2001).
  CAS PubMed Google Scholar
• Dodge, K. & Scott, J. D. AKAP79 and the evolution of the AKAP model. FEBS Lett. 476, 58–61 (2000).
  CAS PubMed Google Scholar
• Fraser, I. D. et al. Assembly of an A kinase-anchoring protein–β(2)-adrenergic receptor complex facilitates receptor phosphorylation and signaling. Curr. Biol. 10, 409–412 (2000).
  CAS PubMed Google Scholar
• Shih, M. et al. Dynamic complexes of β-adrenergic receptors with protein kinases and phosphatases and the role of gravin. J. Biol. Chem. 274, 1588–1595 (1999).
  CAS PubMed Google Scholar
• Diviani, D., Soderling, J. & Scott, J. D. AKAP-Lbc anchors protein kinase A and nucleates Gα12-selective Rho-mediated stress fiber formation. J. Biol. Chem. 276, 44247–44257 (2001).
  CAS PubMed Google Scholar
• Tsunoda, S. et al. A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade. Nature 388, 243–249 (1997).
  CAS PubMed Google Scholar
• Brakeman, P. R. et al. Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 386, 284–288 (1997).
  CAS PubMed Google Scholar
• Cao, W. et al. Direct binding of activated c-Src to the β3-adrenergic receptor is required for MAP kinase activation. J. Biol. Chem. 275, 38131–38134 (2000).
  CAS PubMed Google Scholar
• Marrero, M. B. et al. Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor. Nature 375, 247–250 (1995).
  CAS PubMed Google Scholar
• Hall, R. et al. The β2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. Nature 392, 626–630 (1998).
  CAS PubMed Google Scholar
• Hall, R. A. et al. A C-terminal motif found in the β2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins. Proc. Natl Acad. Sci. USA 95, 8496–8501 (1998).
  CAS PubMed PubMed Central Google Scholar
• Hu, L. A. et al. β1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of β1-adrenergic receptor interaction with _N_-methyl-d-aspartate receptors. J. Biol. Chem. 275, 38659–38666 (2000).
  CAS PubMed Google Scholar
• Sheng, M. & Sala, C. PDZ domains and the organization of supramolecular complexes. Annu. Rev. Neurosci. 24, 1–29 (2001).An authoritative review of a mechanism of protein–protein interactions that regulates several GPCR interactions.
  CAS PubMed Google Scholar
• Luttrell, L. M. et al. β-Arrestin-dependent formation of β2 adrenergic receptor Src protein kinase complexes. Science 283, 655–661 (1999).
  CAS PubMed Google Scholar
• Imamura, T. et al. β-Arrestin-mediated recruitment of the Src family kinase Yes mediates endothelin-1-stimulated glucose transport. J. Biol. Chem. 276, 43663–43667 (2001).
  CAS PubMed Google Scholar
• Barlic, J. et al. Regulation of tyrosine kinase activation and granule release through β-arrestin by CXCR1. Nature Immunol. 1, 227–233 (2000).
  CAS Google Scholar
• DeFea, K. A. et al. β-Arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J. Cell Biol. 148, 1267–1281 (2000).Describes a role for β-arrestin in mediating ERK activation by 7TM receptors.
  CAS PubMed PubMed Central Google Scholar
• Luttrell, L. M. et al. Activation and targeting of extracellular signal-regulated kinases by β-arrestin scaffolds. Proc. Natl Acad. Sci. USA 98, 2449–2454 (2001).
  CAS PubMed PubMed Central Google Scholar
• McDonald, P. H. et al. β-Arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 290, 1574–1577 (2000).
  CAS PubMed Google Scholar
• Tohgo, A. et al. β-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation. J. Biol. Chem. 277, 9429–9436 (2002).
  CAS PubMed Google Scholar
• Cerione, R. A. et al. Reconstitution of a hormone-sensitive adenylate cyclase system. The pure β-adrenergic receptor and guanine nucleotide regulatory protein confer hormone responsiveness on the resolved catalytic unit. J. Biol. Chem. 259, 9979–9982 (1984).
  CAS PubMed Google Scholar
• Cerione, R. A. et al. The mammalian β2-adrenergic receptor: reconstitution of functional interactions between pure receptor and pure stimulatory nucleotide binding protein of the adenylate cyclase system. Biochemistry 23, 4519–4525 (1984).
  CAS PubMed Google Scholar
• Heldin, C. H. Dimerization of cell surface receptors in signal transduction. Cell 80, 213–223 (1995).
  CAS PubMed Google Scholar
• Jordan, B. A. & Devi, L. A. G-protein-coupled receptor heterodimerization modulates receptor function. Nature 399, 697–700 (1999).
  CAS PubMed PubMed Central Google Scholar
• Devi, L. A. Heterodimerization of G-protein-coupled receptors: pharmacology, signaling and trafficking. Trends Pharmacol. Sci. 22, 532–537 (2001).
  CAS PubMed Google Scholar
• Salahpour, A., Angers, S. & Bouvier, M. Functional significance of oligomerization of G-protein-coupled receptors. Trends Endocrinol. Metab. 11, 163–168 (2000).
  CAS PubMed Google Scholar
• Galvez, T. et al. Allosteric interactions between GB1 and GB2 subunits are required for optimal GABAB receptor function. EMBO J. 20, 2152–2159 (2001).
  CAS PubMed PubMed Central Google Scholar
• Nelson, G. et al. An amino-acid taste receptor. Nature 416, 199–202 (2002).
  CAS PubMed Google Scholar
• Nelson, G. et al. Mammalian sweet taste receptors. Cell 106, 381–390 (2001).
  CAS PubMed Google Scholar
• McLatchie, L. M. et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393, 333–339 (1998).
  CAS PubMed Google Scholar
• Kuwasako, K. et al. Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling. J. Biol. Chem. 275, 29602–29609 (2000).
  CAS PubMed Google Scholar
• Hilairet, S. et al. Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and β-arrestin. J. Biol. Chem. 276, 42182–42190 (2001).
  CAS PubMed Google Scholar
• Dean, M. K. et al. Dimerization of G-protein-coupled receptors. J. Med. Chem. 44, 4595–4614 (2001).
  CAS PubMed Google Scholar
• Gilman, A. Please check EGO at door. Mol. Interventions 1, 14–21 (2001).
  CAS Google Scholar
• Brzostowski, J. A. & Kimmel, A. R. Signaling at zero G: G-protein-independent functions for 7-TM receptors. Trends Biochem. Sci. 26, 291–297 (2001).Reviews G-protein-independent signalling by 7TM receptors.
  CAS PubMed Google Scholar
• Zheng, B. et al. RGS-PX1, a GAP for GαS and sorting nexin in vesicular trafficking. Science 294, 1939–1942 (2001).
  CAS PubMed Google Scholar
• Ma, Y. C. et al. Src tyrosine kinase is a novel direct effector of G proteins. Cell 102, 635–646 (2000).
  CAS PubMed Google Scholar
• McLaughlin, S. K., McKinnon, P. J. & Margolskee, R. F. Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature 357, 563–569 (1992).
  CAS PubMed Google Scholar
• Kwok-Keung Fung, B. & Stryer, L. Photolyzed rhodopsin catalyzes the exchange of GTP for bound GDP in retinal rod outer segments. Proc. Natl Acad. Sci. USA 77, 2500–2504 (1980).
  CAS PubMed PubMed Central Google Scholar
• Meng, J., Glick, J. L., Polakis, P. & Casey, P. J. Functional interaction between Gαz and Rap1GAP suggests a novel form of cellular cross-talk. J. Biol. Chem. 274, 36663–36669 (1999).
  CAS PubMed Google Scholar
• Katada, T. et al. The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Properties and function of the purified protein. J. Biol. Chem. 259, 3568–3577 (1984).
  CAS PubMed Google Scholar
• Bokoch, G. M. et al. Purification and properties of the inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. J. Biol. Chem. 259, 3560–3567 (1984).
  CAS PubMed Google Scholar
• Chikumi, H. et al. Potent activation of RhoA by Gαq and Gq-coupled receptors. J. Biol. Chem. 277, 27130–27134 (2002).
  CAS PubMed Google Scholar
• Booden, M. A., Siderovski, D. P. & Der, C. J. Leukemia-associated Rho guanine nucleotide exchange factor promotes Gαq-coupled activation of RhoA. Mol. Cell. Biol. 22, 4053–4061 (2002).
  CAS PubMed PubMed Central Google Scholar
• Smrcka, A. V., Hepler, J. R., Brown, K. O. & Sternweis, P. C. Regulation of polyphosphoinositide-specific phospholipase C activity by purified Gq . Science 251, 804–807 (1991).
  CAS PubMed Google Scholar
• Meigs, T. E., Fields, T. A., McKee, D. D. & Casey, P. J. Interaction of Gα12 and Gα13 with the cytoplasmic domain of cadherin provides a mechanism for β-catenin release. Proc. Natl Acad. Sci. USA 98, 519–524 (2001).
  CAS PubMed PubMed Central Google Scholar
• Kozasa, T. et al. p115 RhoGEF, a GTPase activating protein for Gα12 and Gα13 . Science 280, 2109–2111 (1998).
  CAS PubMed Google Scholar
• Boyer, J. L., Waldo, G. L. & Harden, T. K. βγ-Subunit activation of G-protein-regulated phospholipase C. J. Biol. Chem. 267, 25451–25456 (1992).
  CAS PubMed Google Scholar
• Camps, M. et al. Isozyme-selective stimulation of phospholipase C-β2 by G protein βγ-subunits. Nature 360, 684–686 (1992).
  CAS PubMed Google Scholar
• Pitcher, J. A. et al. Role of βγ subunits of G proteins in targeting the β-adrenergic receptor kinase to membrane-bound receptors. Science 257, 1264–1267 (1992).
  CAS PubMed Google Scholar
• Tang, W. J. & Gilman, A. G. Type-specific regulation of adenylyl cyclase by G protein βγ subunits. Science 254, 1500–1503 (1991).
  CAS PubMed Google Scholar
• Stephens, L. et al. A novel phosphoinositide 3 kinase activity in myeloid-derived cells is activated by G protein βγ subunits. Cell 77, 83–93 (1994).
  CAS PubMed Google Scholar
• Logothetis, D. E. et al. The βγ subunits of GTP-binding proteins activate the muscarinic K+ channel in heart. Nature 325, 321–326 (1987).The first demonstration in a mammalian system of the then-radical idea that G-protein βγ dimers could directly activate effectors.
  CAS PubMed Google Scholar
• Chen, C. K. et al. Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase. Proc. Natl Acad. Sci. USA 96, 3718–3722 (1999).
  CAS PubMed PubMed Central Google Scholar
• Jaber, M. et al. Essential role of β-adrenergic receptor kinase 1 in cardiac development and function. Proc. Natl Acad. Sci. USA 93, 12974–12979 (1996).
  CAS PubMed PubMed Central Google Scholar
• Rockman, H. A. et al. Expression of a β-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc. Natl Acad. Sci. USA 95, 7000–7005 (1998).
  CAS PubMed PubMed Central Google Scholar
• Peppel, K. et al. G protein-coupled receptor kinase 3 (GRK3) gene disruption leads to loss of odorant receptor desensitization. J. Biol. Chem. 272, 25425–25428 (1997).
  CAS PubMed Google Scholar
• Walker, J. K. et al. Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3. Am. J. Physiol. 276, R1214–R1221 (1999).
  CAS PubMed Google Scholar
• Gainetdinov, R. R. et al. Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice. Neuron 24, 1029–1036 (1999).
  CAS PubMed Google Scholar
• Fong, A. M. et al. Defective lymphocyte chemotaxis in β-arrestin2- and GRK6-deficient mice. Proc. Natl Acad. Sci. USA 99, 7478–7483 (2002).
  CAS PubMed PubMed Central Google Scholar
• Conner, D. A. et al. β-Arrestin1 knockout mice appear normal but demonstrate altered cardiac responses to β-adrenergic stimulation. Circ. Res. 81, 1021–1026 (1997).
  CAS PubMed Google Scholar
• Bohn, L. M. et al. Enhanced morphine analgesia in mice lacking β-arrestin 2. Science 286, 2495–2498 (1999).
  CAS PubMed Google Scholar
• Bohn, L. M. et al. μ-Opioid receptor desensitization by β-arrestin-2 determines morphine tolerance but not dependence. Nature 408, 720–723 (2000).
  CAS PubMed Google Scholar
• Dohlman, H. G. & Thorner, J. W. Regulation of G protein-initiated signal transduction in yeast: paradigms and principles. Annu. Rev. Biochem. 70, 703–754 (2001).
  CAS PubMed Google Scholar