Abstract
The octapeptide angiotensin II (Ang II) binds to two subtypes of receptors, AT1 and AT2, that both belong to the superfamily of G protein-coupled receptors (GPCRs). The AT1 subtype is a classical GPCR in terms of coupling and signaling, and appears to mediate all known physiological actions of Ang II. In contrast, the AT2 subtype is an atypical receptor that has remained a puzzle since its discovery in 1989 and molecular cloning in 1993. Over the past 10 years, a number of studies have aimed at elucidating the signaling pathways and functions of the AT2 subtype. A role for AT2 receptors has been established during fetal development and in cardiovascular, brain, and renal functions. In most cases, the AT2 receptor has been shown to counteract the effects of the AT1 subtype. AT2 also negatively cross-talks with growth factor receptors and plays a major role in the processes of apoptosis, migration, differentiation, and tissue regeneration. Depending on the cellular model and function examined, the AT2 receptor activates different signaling pathways, that can be classified into three major types: regulation of protein phosphorylation, activation of phospholipases, and/or regulation of nitric oxide (NO)/cGMP. In the present chapter, we review recent advances on the molecular aspects of the AT2 receptor: its structural features (functional domains involved in ligand binding and receptor activation), signaling pathways, coupling to G proteins and association with other intracellular partners. We then examine the molecular mechanisms by which AT2 antagonizes the effects of the AT1 subtype. Examples of AT2 receptor gene alterations associated with human diseases such as congenital anomalies of kidney and urinary tract (CAKUT) or X-linked mental retardation, are also discussed.
Keywords
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
AbdAlla S, Lother H, Abdel-tawab A, Quitterer U (2001) The angiotensin II AT2 receptor is an AT1 receptor antagonist. J Biol Chem 276:39721–39726
Bedecs K, Elbaz N, Sutren M, Masson M, Susini C, Strosberg A, Nahmias C (1997) Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase. Biochem J 325:449–454
Bottari S, Taylor V, King I, Bogdal Y, Whitebread S, Gasparo Md (1991) Angiotensin II AT2 receptors do not interact with guanine nucleotide binding proteins. Eur J Pharmacol 207:157–163
Bottari S, King I, Reichlin S, Dahlstroem I, Lydon N, Gasparo Md (1992) The angiotensin AT2 receptor stimulates protein tyrosine phosphatase activity and mediates inhibition of particulate guanylate cyclase. Biochem Biophys Res Commun 183:206–211
Brady A, Limbird L (2002) G protein-coupled receptor interacting proteins: emerging roles in localization and signal transduction. Cell Signal 14:297–309
Braszko J (2002) AT(2) but not AT(1) receptor antagonism abolishes angiotensin II increase of the acquisition of conditioned avoidance responses in rats. Behav Brain Res 131:79–86
Brechler V, Reichlin S, Gasparo MD, Bottari S (1994) Angiotensin II stimulates protein tyrosine phosphatase activity through a G-protein independent mechanism. Receptors Channels 2:89–98
Brede M, Hadamek K, Meinel L, Wiesmann F, Peters J, Engelhardt S, Simm A, Haase A, Lohse M, Hein L (2001) Vascular hypertrophy and increased P70S6 kinase in mice lacking the angiotensin II AT(2) receptor. Circulation 104:2602–2607
Buisson B, Laflamme L, Bottari S, Gasparo Md, Gallo-Payet N, Payet M (1995) A G protein is involved in the angiotensin AT2 receptor inhibition of the T-type calcium current in non-differentiated NG108-15 cells. J Biol Chem 270:1670–1674
Carey R, Jin X, Wang Z, Siragy H (2000) Nitric oxide: a physiological mediator of the type 2 (AT2) angiotensin receptor. Acta Physiol Scand 168:65–71
Chassagne C, Adamy C, Ratajczak P, Gingras B, Teiger E, Planus E, Oliviero P, Rappaport L, Samuel J, Meloche S (2002) Angiotensin II AT(2) receptor inhibits smooth muscle cell migration via fibronectin cell production and binding. Am J Physiol Cell Physiol 282:C654–C664
Chiu A, Herblin W, McCall D, Ardecky R, Carini D, Duncia J, Pease L, Wong P, Wexler R, AL AJ (1989a) Identification of angiotensin II receptor subtypes. Biochem Biophys Res Commun 165:196–203
Chiu A, McCall D, Nguyen T, Carini D, Duncia J, Herblin W, Uyeda R, Wong P, Wexler R, Johnson A (1989b) Discrimination of angiotensin II receptor subtypes by dithiothre-itol. Eur J Pharmacol 170:117–118
Cote F, Laflamme L, Payet M, Gallo-Payet N (1998) Nitric oxide, a new second messenger involved in the action of angiotensin II on neuronal differentiation of NG108-15 cells. Endocr Res 24:403–407
Cote F, Do T, Laflamme L, Gallo J, Gallo-Payet N (1999) Activation of the AT(2) receptor of angiotensin II induces neurite outgrowth and cell migration in microexplant cultures of the cerebellum. J Biol Chem 274:31686–31692
Cui T, Nakagami H, Iwai M, Takeda Y, Shiuchi T, Tamura K, Daviet L, Horiuchi M (2000) ATRAP, novel AT] receptor associated protein, enhances internalization of AT1 receptor and inhibits vascular smooth muscle cell growth. Biochem Biophys Res Commun 279:938–941
Cui T, Nakagami H, Iwai M, Takeda Y, Shiuchi T, Daviet L, Nahmias C, Horiuchi M (2001) Pivotal role of tyrosine phosphatase SHP-1 in AT2 receptor-mediated apoptosis in rat fetal vascular smooth muscle cell. Cardiovasc Res 49:863–871
Cui T, Nakagami H, Nahmias C, Shiuchi T, Takeda-Matsubara Y, Li J, Wu L, Iwai M, Horiuchi M (2002) Angiotensin II Subtype 2 Receptor Activation Inhibits Insulin-Induced Phosphoinositide 3-Kinase and Akt and Induces Apoptosis in PC12W Cells. Mol Endocrinol 16:2113–2123
Daviet L, Lehtonen J, Tamura K, Griese D, Horiuchi M, Dzau V (1999) Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor. J Biol Chem 274:17058–17062
Daviet L, Lehtonen J, Hayashida W, Dzau V, Horiuchi M (2001) Intracellular third loops in AT1 and AT2 receptors determine subtype specificity. Life Sci 69:509–516
DePaolis P, Porcellini A, Savoia C, Lombardi A, Gigante B, Frati G, Rubattu S, Musumeci B, Volpe M (2002) Functional cross-talk between angiotensin II and epidermal growth factor receptors in NIH3T3 fibroblasts. J Hypertens 20:693–699
Deraet M, Rihakova L, Boucard A, Perodin J, Sauve S, Mathieu A, Guillemette G, Leduc R, Lavigne P, Escher E (2002) Angiotensin II is bound to both receptors AT1 and AT2, parallel to the transmembrane domains and in an extended form. Can J Physiol Pharmacol 80:418–425
Dittus J, Cooper S, Obermair G, Pulakat L, Obermeir G (1999) Role of the third intracellular loop of the angiotensin II receptor subtype AT2 in ligand-receptor interaction. FEBS Lett 445:23–26
Dulin N, Alexander L, Harwalkar S, Falck J, Douglas J (1998) Phospholipase A2-mediated activation of mitogen-activated protein kinase by angiotensin II. Proc Natl Acad Sci USA 95:8098–8102
Elbaz N, Bedecs K, Masson M, Sutren M, Strosberg AD, Nahmias C (2000) Functional trans-inactivation of insulin receptor kinase by growth-inhibitory angiotensin II AT2 receptor. Mol Endocrinol 14:795–804
Feng Y, Saad Y, Karnik SS (2000) Reversible inactivation of AT(2) angiotensin II receptor from cysteine-disulfide bond exchange. FEBS Lett 484:133–138
Feng Y, Sun Y, Douglas J (2002) Gβγ-independent constitutive association of Gas with SHP-1 and angiotensin II receptor AT2 is essential in AT2-mediated ITIM-indepen-dent activation of SHP-1. Proc Natl Acad Sci USA 99:12049–12054
Fischer J, Stoll M, Hahn A, Unger T (2001) Differential regulation of thrombospondin-1 and fibronectin by angiotensin II receptor subtypes in cultured endothelial cells. Cardiovasc Res 51:784–791
Gallinat S, Csikos T, Meffert S, Herdegen T, Stoll M, Unger T (1997) The angiotensin AT2 receptor down-regulates neurofilament M in PC12W cells. Neurosci Lett 227:29–32
Gallinat S, Busche S, Schutze S, Kronke M, Unger T (1999) AT2 receptor stimulation induces generation of ceramides in PC12W cells. FEBS Lett 443:75–79
Gelband C, Zhu M, Lu D, Reagan L, Fluharty S, Posner P, Raizada M, Sumners C (1997) Functional interactions between neuronal AT1 and AT2 receptors. Endocrinology 138:2195–2198
Gendron L, Laflamme L, Asselin C, Payet M, Gallo-Payet N (1998) A role for p21ras in the angiotensin II AT2 receptor transduction pathway. Endocr Res 24:409–412
Gendron L, Laflamme L, Rivard N, Asselin C, Payet M, Gallo-Payet N (1999) Signals from the AT2 (angiotensin type 2) receptor of angiotensin II inhibit p21ras and activate MAPK (mitogen-activated protein kinase) to induce morphological neuronal differentiation in NG108-15 cells. Mol Endocrinol 13:1615–1626
Gendron L, Cote F, Payet M, Gallo-Payet N (2002) Nitric oxide and cyclic GMP are involved in angiotensin II AT(2) receptor effects on neurite outgrowth in NG108-15 cells. Neuroendocrinology 75:70–81
Gohlke P, Pees C, linger T (1998) AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. Hypertension 31:349–355
Hackel P, Zwick E, Prenzel N, Ullrich A (1999) Epidermal growth factor receptors: critical mediators of multiple receptor pathways. Curr Opin Cell Biol 11:184–189
Hansen J, Servant G, Baranski T, Fujita T, Iiri T, Sheikh S (2000) Functional reconstitution of the angiotensin II type 2 receptor and G(i) activation. Circ Res 87:753–759
Harwalkar S, Chang C, Dulin N, Douglas J (1998) Role of phospholipase A2 isozymes in agonist-mediated signaling in proximal tubular epithelium. Hypertension 31:809–814
Hayashida W, Horiuchi M, Dzau V (1996) Intracellular third loop domain of angiotensin II type-2 receptor. Role in mediating signal transduction and cellular function. J Biol Chem 271:21985–21992
Heerding J, Yee D, Jacobs S, Fluharty S (1997) Mutational analysis of the angiotensin II type 2 receptor: contribution of conserved extracellular amino acids. Regul Pept 72:97–103
Heerding J, Yee D, Krichavsky M, Fluharty S (1998) Mutational analysis of the angiotensin type 2 receptor: contribution of conserved amino acids in the region of the sixth transmembrane domain. Regul Pept 74:113–119
Heerding J, Hines J, Fluharty S, Yee D (2001) Identification and function of disulfide bridges in the extracellular domains of the angiotensin II type 2 receptor. Biochemistry 40:8369–8377
Hein L, Barsh G, Pratt R, Dzau V, Kobilka B (1995) Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Nature 377:744–747
Hines J, Fluharty S, Yee D (2001a) Chimeric AT1/AT2 receptors reveal functional similarities despite key amino acid dissimilarities in the domains mediating agonist-dependent activation. Biochemistry 40:11251–11260
Hines J, Heerding J, Fluharty S, Yee D (2001b) Identification of angiotensin II type 2 (AT2) receptor domains mediating high-affinity CGP 42112A binding and receptor activation. J Pharmacol Exp Ther 298:665–673
Hiraoka M, Taniguchi T, Nakai H, Kino M, Okada Y, Tanizawa A, Tsukahara H, Ohshima Y, Muramatsu I, Mayumi M (2001) No evidence for AT2R gene derangement in human urinary tract anomalies. Kidney Int 59:1244–1249
Horiuchi M, Hayashida W, Kambe T, Yamada T, Dzau V (1997) Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phospha-tase-1 and induces apoptosis. J Biol Chem 272:19022–19026
Horiuchi M, Hayashida W, Akishita M, Tamura K, Daviet L, Lehtonen J, Dzau V (1999a) Stimulation of different subtypes of angiotensin II receptors, AT1 and AT2 receptors, regulates STAT activation by negative crosstalk. Circ Res 84:876–882
Horiuchi M, Lehtonen J, Daviet L (1999b) Signaling Mechanism of the AT2 Angiotensin II Receptor: Crosstalk between AT1 and AT2 Receptors in Cell Growth. Trends Endocrinol Metab 10:391–396
Huang X, Richards E, Sumners C (1995) Angiotensin II type 2 receptor-mediated stimulation of protein phosphatase 2A in rat hypothalamic/brainstem neuronal cocultures. J Neurochem 65:2131–2137
Huang X, Richards E, Sumners C (1996) Mitogen-activated protein kinases in rat brain neuronal cultures are activated by angiotensin II type 1 receptors and inhibited by angiotensin II type 2 receptors. J Biol Chem 271:15635–15641
Ichiki T, Labosky P, Shiota C, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan B, Inagami T (1995) Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature 377:748–750
Jacobs L, Douglas J (1996) Angiotensin II type 2 receptor subtype mediates phospholi-pase A2-dependent signaling in rabbit proximal tubular epithelial cells. Hypertension 28:663–668
Jiao H, Cui X, Torti M, Chang C, Alexander L, Lapetina E, Douglas J (1998) Arachidonic acid mediates angiotensin II effects on p21ras in renal proximal tubular cells via the tyrosine kinase-Shc-Grb2-Sos pathway. Proc Natl Acad Sci USA 95:7417–7421
Kang J, Posner P, Sumners C (1994) Angiotensin II type 2 receptor stimulation of neuronal K+ currents involves an inhibitory GTP binding protein. Am J Physiol 267:1389–1397
Kang J, Richards E, Posner P, Sumners C (1995) Modulation of the delayed rectifier K+ current in neurons by an angiotensin II type 2 receptor fragment. Am J Physiol 268:C278–C282
Knowle D, Ahmed S, Pulakat L (2000) Identification of an interaction between the angiotensin II receptor sub-type AT2 and the ErbB3 receptor, a member of the epidermal growth factor receptor family. Regul Pept 87:73–82
Knowle D, Kurfis J, Gavini N, Pulakat L (2001) Role of Asp297 of the AT2 receptor in high-affinity binding to different peptide ligands. Peptides 22:2145–2149
Kohagura K, Endo Y, Ito O, Arima S, Omata K, Ito S (2000) Endogenous nitric oxide and epoxyeicosatrienoic acids modulate angiotensin II-induced constriction in the rabbit afferent arteriole. Acta Physiol Scand 168:107–112
Kurfis J, Knowle DK, Pulakat L (1999) Role of Arg 182 in the second extracellular loop of angiotensin II receptor AT2 in ligand binding. Biochem Biophys Res Commun 263:816–819
Laflamme L, Gasparo M, Gallo J, Payet M, Gallo-Payet N (1996) Angiotensin II induction of neurite outgrowth by AT2 receptors in NG108-15 cells. Effect counteracted by the AT1 receptors. J Biol Chem 271:22729–22735
Lazard D, Briend-Sutren M, Villageois P, Mattei M, Strosberg A, Nahmias C (1994a) Molecular characterization and chromosome localization of a human angiotensin II AT2 receptor gene highly expressed in fetal tissues. Receptors Channels 2:271–280
Lazard D, Villageois P, Briend-Sutren M, Cavaille F, Bottari S, Strosberg A, Nahmias C (1994b) Characterization of a membrane glycoprotein having pharmacological and biochemical properties of an AT2 angiotensin II receptor from human myometrium. Eur J Biochem 220:919–926
Lehtonen J, Daviet L, Nahmias C, Horiuchi M, Dzau V (1999a) Analysis of functional domains of angiotensin II type 2 receptor involved in apoptosis. Mol Endocrinol 13:1051–1060
Lehtonen J, Horiuchi M, Daviet L, Akishita M, Dzau V (1999b) Activation of the de novo biosynthesis of sphingolipids mediates angiotensin II type 2 receptor-induced apoptosis. J Biol Chem 274:16901–16906
Lopez F, Esteve J, Buscail L, Delesque N, Saint-Laurent N, Theveniau M, Nahmias C, Vaysse N, Susini C (1997) The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling. J Biol Chem 272:24448–24454
Lucius R, Gallinat S, Rosenstiel P, Herdegen T, Sievers J, Unger T (1998) The angiotensin II type 2 (AT2) receptor promotes axonal regeneration in the optic nerve of adult rats. J Exp Med 188:661–670
Marinissen M, Gutkind J (2001) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol Sci 22:368–376
Marrero M, Venema V, Ju H, Eaton D, Venema R (1998) Regulation of angiotensin II-in-duced JAK2 tyrosine phosphorylation: roles of SHP-1 and SHP-2. Am J Physiol 275:C1216–C1223
Martens J, Wang D, Sumners C, Posner P, Gelband C (1996) Angiotensin II type 2 receptor-mediated regulation of rat neuronal K+ channels. Circ Res 79:302–309
Martin M, Elton T (1995) The sequence and genomic organization of the human type 2 angiotensin II receptor. Biochem Biophys Res Commun 209:554–562
Masaki H, Kurihara T, Yamaki A, Inomata N, Nozawa Y, Mori Y, Murasawa S, Kizima K, Maruyama K, Horiuchi M, Dzau V, Takahashi H, Iwasaka T, Inada M, Matsubara H (1998) Cardiac-specific overexpression of angiotensin II AT2 receptor causes attenuated response to AT1 receptor-mediated pressor and chronotropic effects. J Clin Invest 101:527–535
Matsubara H, Shibasaki Y, Okigaki M, Mori Y, Masaki H, Kosaki A, Tsutsumi Y, Uchiyama Y, Fujiyama S, Nose A, Iba O, Tateishi E, Hasegawa T, Horiuchi M, Nahmias C, Iwasaka T (2001) Effect of angiotensin II type 2 receptor on tyrosine kinase Pyk2 and c-Jun NH2-terminal kinase via SHP-1 tyrosine phosphatase activity: evidence from vascular-targeted transgenic mice of AT2 receptor. Biochem Biophys Res Commun 282:1085–1089
Meffert S, Stoll M, Steckelings U, Bottari S, Unger T (1996) The angiotensin II AT2 receptor inhibits proliferation and promotes differentiation in PC12W cells. Mol Cell Endocrinol 122:59–67
Mifune M, Sasamura H, Shimizu-Hirota R, Miyazaki H, Saruta T (2000) Angiotensin II type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells. Hypertension 36:845–850
Miura S, Karnik S (1999) Angiotensin II type 1 and type 2 receptors bind angiotensin II through different types of epitope recognition. J Hypertens 17:397–404
Miura S, Karnik S (2000) Ligand-independent signals from angiotensin II type 2 receptor induce apoptosis. EMBO J 19:4026–4035
Nahmias C, Cazaubon S, Briend-Sutren M, Lazard D, Villageois P, Strosberg A (1995) Angiotensin II AT2 receptors are functionally coupled to protein tyrosine dephosphory-lation in N1E-115 neuroblastoma cells. Biochem J 306:87–92
Nishimura H, Yerkes E, Hohenfellner K, Miyazaki Y, Ma J, Hunley T, Yoshida H, Ichiki T, Threadgill D, Phillips J, Hogan B, Fogo A, Brock J, Inagami T, Ichikawa I (1999) Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men. Mol Cell 3:1–10
Nouet S, Nahmias C (2000) Signal transduction from the angiotensin II AT2 receptor. Trends Endocrinol Metab 11:1–6
Nuyt A, Lenkei Z, Palkovits M, Corvol P, Llorens-Cortes C (1999) Ontogeny of angiotensin II type 2 receptor mRNA expression in fetal and neonatal rat brain. J Comp Neurol 407:193–206
Okuyama S, Sakagawa T, Chaki S, Imagawa Y, Ichiki T, Inagami T (1999) Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor. Brain Res 821:150–159
Olayioye M, Neve R, Lane H, Hynes N (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19:3159–3167
Pulakat L, Tadessee A, Dittus J, Gavini N (1998) Role of Lys215 located in the fifth transmembrane domain of the AT2 receptor in ligand-receptor interaction. Regul Pept 73:51–57
Pulakat L, Gray A, Johnson J, Knowle D, Burns V, Gavini N (2002) Role of C-terminal cytoplasmic domain of the AT2 receptor in ligand binding and signaling. FEBS Lett 524:73–78
Rossig L, Hermann C, Haendeler J, Assmus B, Zeiher A, Dimmeier S (2002) Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels mediates endothelial cell apotosis. Basic Res Cardiol 97:1–8
Salahpour A, Angers S, Bouvier M (2000) Functional significance of oligomerization of G-protein-coupled receptors. Trends Endocrinol Metab 11:163–168
Sasamura H, Mifune M, Nakaya H, Amemiya T, Hiraki T, Nishimoto I, Saruta T (2000) Analysis of Galpha protein recognition profiles of angiotensin II receptors using chimeric Galpha proteins. Mol Cell Endocrinol 170:113–121
Schelman W, Kurth J, Berdeaux R, Norby S, Weyhenmeyer J (1997) Angiotensin II type-2 (AT2) receptor-mediated inhibition of NMDA receptor signaling in neuronal cells. Brain Res Mol Brain Res 48:197–205
Servant G, Dudley D, Escher E, Guillemette G (1996) Analysis of the role of N-glycosylation in cell-surface expression and binding properties of angiotensin II type-2 receptor of rat pheochromocytoma cells. Biochem J 313:297–304
Servant G, Laporte S, Leduc R, Escher E, Guillemette G (1997) Identification of angiotensin Il-binding domains in the rat AT2 receptor with photolabile angiotensin analogs. J Biol Chem 272:8653–8659
Shenoy U, Richards E, Huang X, Sumners C (1999) Angiotensin II type 2 receptor-mediated apoptosis of cultured neurons from newborn rat brain. Endocrinology 140:500–509
Shibasaki Y, Matsubara H, Nozawa Y, Mori Y, Masaki H, Kosaki A, Tsutsumi Y, Uchiyama Y, Fujiyama S, Nose A, Iba O, Tateishi E, Hasegawa T, Horiuchi M, Nahmias C, Iwasaka T (2001) Angiotensin II type 2 receptor inhibits epidermal growth factor receptor transactivation by increasing association of SHP-1 tyrosine phosphatase. Hypertension 38:367–372
Siragy H, Carey R (1997) The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. J Clin Invest 100:264–269
Siragy H, Inagami T, Ichiki T, Carey R (1999) Sustained hypersensitivity to angiotensin II and its mechanism in mice lacking the subtype-2 (AT2) angiotensin receptor. Proc Natl Acad Sci USA 96:6506–6510
Sohn H, Raff U, Hoffmann A, Gloe T, Heermeier K, Galle J, Pohl U (2000) Differential role of angiotensin II receptor subtypes on endothelial superoxide formation. Br J Pharmacol 131:667–672
Stoll M, Unger T (2001) Angiotensin and its AT2 receptor: new insights into an old system. Regul Pept 99:175–182
Stroth U, Meffert S, Gallinat S, Unger T (1998) Angiotensin II and NGF differentially influence microtubule proteins in PC12W cells: role of the AT2 receptor. Brain Res Mol Brain Res 53:187–195
Stroth U, Blume A, Mielke K, Unger T (2000) Angiotensin AT(2) receptor stimulates ERK1 and ERK2 in quiescent but inhibits ERK in NGF-stimulated PC12W cells. Brain Res Mol Brain Res 78:175–180
Sumners C, Gelband C (1998) Neuronal ion channel signalling pathways: modulation by angiotensin II. Cell Signal 10:303–311
Turner C, Cooper S, Pulakat L (1999) Role of the His273 located in the sixth transmembrane domain of the angiotensin II receptor subtype AT2 in ligand-receptor interaction. Biochem Biophys Res Commun 257:704–707
Unger T (1999) The angiotensin type 2 receptor: variations on an enigmatic theme. J Hypertens 17:1775–1786
Vervoort V, Beachem M, Edwards P, Ladd S, Miller K, Mollerat X, Clarkson K, DuPont B, Schwartz C, Stevenson R, Boyd E, Srivastava AK (2002) AGTR2 mutations in X-linked mental retardation. Science 296:2401–2403
Wang C, Jayadev S, Escobedo J (1995) Identification of a domain in the angiotensin II type 1 receptor determining Gq coupling by the use of receptor chimeras. J Biol Chem 270:16677–16682
Warnecke C, Surder D, Curth R, Fleck E, Regitz-Zagrosek V (1999a) Analysis and functional characterization of alternatively spliced angiotensin II type 1 and 2 receptor transcripts in the human heart. J Mol Med 77:718–727
Warnecke C, Willich T, Holzmeister J, Bottari S, Fleck E, Regitz-Zagrosek V (1999b) Efficient transcription of the human angiotensin II type 2 receptor gene requires intronic sequence elements. Biochem J 340:17–24
Yamada H, Akishita M, Ito M, Tamura K, Daviet L, Lehtonen J, Dzau V, Horiuchi M (1999) AT2 receptor and vascular smooth muscle cell differentiation in vascular development. Hypertension 33:1414–1419
Yamada T, Horiuchi M, Dzau V (1996) Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci USA 93:156–160
Yee D, Kisley L, Heerding J, Fluharty S (1997) Mutation of a conserved fifth transmembrane domain lysine residue (Lys215) attenuates ligand binding in the angiotensin II type 2 receptor. Brain Res Mol Brain Res 51:238–241
Yee D, Heerding J, Krichavsky M, Fluharty S (1998) Role of the amino terminus in ligand binding for the angiotensin II type 2 receptor. Brain Res Mol Brain Res 57:325–329
Yoneda A, Cascio S, Green A, Barton D, Puri P (2002) Angiotensin II type 2 receptor gene is not responsible for familial vesicoureteral reflux. J Urol 168:1138–1141
Zhang J, Pratt R (1996) The AT2 receptor selectively associates with Gialpha2 and Gial-pha3 in the rat fetus. J Biol Chem 271:15026–15033
Zhu M, Gelband C, Moore J, Posner P, Sumners C (1998) Angiotensin II type 2 receptor stimulation of neuronal delayed-rectifier potassium current involves phospholipase A2 and arachidonic acid. J Neurosci 18:679–686
Zhu M, Natarajan R, Nadler J, Moore J, Gelband C, Sumners C (2000) Angiotensin II increases neuronal delayed rectifier K(+) current: role of 12-lipoxygenase metabolites of arachidonic acid. J Neurophysiol 84:2494–2501
Zhu M, Sumners C, Gelband C, Posner P (2001) Chronotropic effect of angiotensin II via type 2 receptors in rat brain neurons. J Neurophysiol 85:2177–2183
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Nahmias, C., Boden, C. (2004). Molecular Aspects of AT2 Receptor. In: Unger, T., Schölkens, B.A. (eds) Angiotensin Vol. I. Handbook of Experimental Pharmacology, vol 163 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18495-6_17
Download citation
DOI: https://doi.org/10.1007/978-3-642-18495-6_17
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-40640-2
Online ISBN: 978-3-642-18495-6
eBook Packages: Springer Book Archive