Bradykinin receptor B2

Bradykinin receptor B₂ is a G-protein coupled receptor for bradykinin, encoded by the BDKRB2 gene in humans.

BDKRB2
Identifiers
Aliases	BDKRB2, B2R, BK-2, BK2, BKR2, BRB2, bradykinin receptor B2
External IDs	OMIM: 113503; MGI: 102845; HomoloGene: 519; GeneCards: BDKRB2; OMA:BDKRB2 - orthologs
Gene location (Human) Chr. Chromosome 14 (human) Band 14q32.2 Start 96,204,679 bp End 96,244,166 bp
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12 E|12 55.76 cM Start 105,529,485 bp End 105,561,496 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium mucosa of urinary bladder pancreatic ductal cell tendon of biceps brachii gums cartilage tissue gingival epithelium gallbladder ectocervix canal of the cervix Top expressed in esophagus embryo embryo adrenal gland pituitary gland lip duodenum placenta muscle of thigh ileum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity type 1 angiotensin receptor binding signal transducer activity protease binding protein binding protein heterodimerization activity phosphatidylinositol phospholipase C activity bradykinin receptor activity Cellular component integral component of membrane endosome membrane integral component of plasma membrane plasma membrane Biological process G protein-coupled receptor signaling pathway negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress response to salt stress vasoconstriction transmembrane receptor protein tyrosine kinase signaling pathway response to stress negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator vasodilation blood circulation cell surface receptor signaling pathway regulation of vascular permeability regulation of vasoconstriction negative regulation of peptidyl-serine phosphorylation inflammatory response arachidonic acid secretion signal transduction smooth muscle contraction positive regulation of cytosolic calcium ion concentration Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 624 12062 Ensembl ENSG00000168398 ENSMUSG00000021070 UniProt P30411 P32299 RefSeq (mRNA) NM_000623 NM_001379692 NM_009747 RefSeq (protein) NP_000614 NP_001366621 NP_033877 Location (UCSC) Chr 14: 96.2 – 96.24 Mb Chr 12: 105.53 – 105.56 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Mechanism

The B₂ receptor (B₂R) is a G protein-coupled receptor, probably coupled to G_q and G_i. A 2022 Nature cryo-EM study of human B₂R-G_q complexes by Jinkeng Sheng et al. investigated the proximal activation mechanisms of B₂R. Sheng et al. propose that upon B₂R binding bradykinin or kallidin to a "bulky orthosteric binding pocket," the phenylalanine F8 or F9 residue of bradykinin or kallidin respectively interacts with a "conserved toggle switch" W283. This hydrophobic interaction facilitates the outward movement of transmembrane domain 6 (TM6) of B₂R on the cytoplasmic side of the membrane, as well as outward movement of F279, a key residue within the conserved PIF motif of GPCRs (involving proline, isoleucine and phenylalanine). This rearrangement of the PIF motif disrupts the ionic lock formed by the DRY motif and pushes the NPxxY motif towards the activated state, opening an "intracellular cleft" for insertion of the α5-helix of G_q.

G_q stimulates phospholipase C to increase intracellular free calcium and G_i inhibits adenylate cyclase. Furthermore, the receptor stimulates the mitogen-activated protein kinase pathways. It is ubiquitously and constitutively expressed in healthy tissues.

The B₂ receptor forms a complex with angiotensin converting enzyme (ACE), and this is thought to play a role in cross-talk between the renin-angiotensin system (RAS) and the kinin–kallikrein system (KKS). The heptapeptide angiotensin (1-7) also potentiates bradykinin action on B₂ receptors.

Kallidin also signals through the B₂ receptor. An antagonist for the receptor is Hoe 140 (icatibant).

Function

The 9 amino acid bradykinin peptide elicits several responses including vasodilation, edema, smooth muscle spasm and nociceptor stimulation.

Gene

Alternate start codons result in two isoforms of the protein.

See also

• Bradykinin receptor

Further reading

• Duchêne J, Schanstra J, Cellier E, Bascands JL, Girolami JP (2002). "[30 years: Happy birthday, GPCR. The bradykinin B2 receptor: an alternative and antiproliferative pathway]". Nephrologie. 23 (1): 39–41. PMID 11908480.
• Ariza AC, Bobadilla NA, Halhali A (2007). "[Endothelin 1 and angiotensin II in preeeclampsia]". Revista de Investigacion Clinica. 59 (1): 48–56. PMID 17569300.
• Hess JF, Borkowski JA, Young GS, Strader CD, Ransom RW (April 1992). "Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor". Biochemical and Biophysical Research Communications. 184 (1): 260–268. doi:10.1016/0006-291X(92)91187-U. PMID 1314587.
• Eggerickx D, Raspe E, Bertrand D, Vassart G, Parmentier M (September 1992). "Molecular cloning, functional expression and pharmacological characterization of a human bradykinin B2 receptor gene". Biochemical and Biophysical Research Communications. 187 (3): 1306–1313. doi:10.1016/0006-291X(92)90445-Q. PMID 1329734.
• Kammerer S, Braun A, Arnold N, Roscher AA (June 1995). "The human bradykinin B2 receptor gene: full length cDNA, genomic organization and identification of the regulatory region". Biochemical and Biophysical Research Communications. 211 (1): 226–233. doi:10.1006/bbrc.1995.1800. PMID 7779089.
• Braun A, Kammerer S, Böhme E, Müller B, Roscher AA (June 1995). "Identification of polymorphic sites of the human bradykinin B2 receptor gene". Biochemical and Biophysical Research Communications. 211 (1): 234–240. doi:10.1006/bbrc.1995.1801. PMID 7779090.
• Ma JX, Wang DZ, Ward DC, Chen L, Dessai T, Chao J, et al. (September 1994). "Structure and chromosomal localization of the gene (BDKRB2) encoding human bradykinin B2 receptor". Genomics. 23 (2): 362–369. doi:10.1006/geno.1994.1512. PMID 7835885.
• Powell SJ, Slynn G, Thomas C, Hopkins B, Briggs I, Graham A (February 1993). "Human bradykinin B2 receptor: nucleotide sequence analysis and assignment to chromosome 14". Genomics. 15 (2): 435–438. doi:10.1006/geno.1993.1084. PMID 7916737.
• Menke JG, Borkowski JA, Bierilo KK, MacNeil T, Derrick AW, Schneck KA, et al. (August 1994). "Expression cloning of a human B1 bradykinin receptor". The Journal of Biological Chemistry. 269 (34): 21583–21586. doi:10.1016/S0021-9258(17)31844-6. PMID 8063797.{{cite journal}}: CS1 maint: overridden setting (link)
• Hess JF, Borkowski JA, Macneil T, Stonesifer GY, Fraher J, Strader CD, et al. (January 1994). "Differential pharmacology of cloned human and mouse B2 bradykinin receptors". Molecular Pharmacology. 45 (1): 1–8. PMID 8302267.
• McIntyre P, Phillips E, Skidmore E, Brown M, Webb M (August 1993). "Cloned murine bradykinin receptor exhibits a mixed B1 and B2 pharmacological selectivity". Molecular Pharmacology. 44 (2): 346–355. PMID 8394991.
• AbdAlla S, Godovac-Zimmermann J, Braun A, Roscher AA, Müller-Esterl W, Quitterer U (June 1996). "Structure of the bradykinin B2 receptors' amino terminus". Biochemistry. 35 (23): 7514–7519. doi:10.1021/bi9601060. PMID 8652530.
• Isami S, Kishikawa H, Araki E, Uehara M, Kaneko K, Shirotani T, et al. (April 1996). "Bradykinin enhances GLUT4 translocation through the increase of insulin receptor tyrosine kinase in primary adipocytes: evidence that bradykinin stimulates the insulin signalling pathway". Diabetologia. 39 (4): 412–420. doi:10.1007/BF00400672. PMID 8777990. S2CID 2243985.{{cite journal}}: CS1 maint: overridden setting (link)
• Dalemar LR, Ivy Jong YJ, Wilhelm B, Baenziger NL (March 1996). "Protein kinases A and C rapidly modulate expression of human lung fibroblast B2 bradykinin receptor affinity forms". European Journal of Cell Biology. 69 (3): 236–244. PMID 8900488.
• Soskic V, Nyakatura E, Roos M, Müller-Esterl W, Godovac-Zimmermann J (March 1999). "Correlations in palmitoylation and multiple phosphorylation of rat bradykinin B2 receptor in Chinese hamster ovary cells". The Journal of Biological Chemistry. 274 (13): 8539–8545. doi:10.1074/jbc.274.13.8539. PMID 10085087.
• Cassano G, Susca F, Lippe C, Guanti G (February 1999). "Two B1 and B2 bradykinin receptor antagonists fail to inhibit the Ca2+ response elicited by bradykinin in human skin fibroblasts". General Pharmacology. 32 (2): 239–244. doi:10.1016/S0306-3623(98)00275-4. PMID 10188626.
• Efremov R, Truong MJ, Darcissac EC, Zeng J, Grau O, Vergoten G, et al. (August 1999). "Human chemokine receptors CCR5, CCR3 and CCR2B share common polarity motif in the first extracellular loop with other human G-protein coupled receptors implications for HIV-1 coreceptor function". European Journal of Biochemistry. 263 (3): 746–756. doi:10.1046/j.1432-1327.1999.00553.x. PMID 10469138.{{cite journal}}: CS1 maint: overridden setting (link)
• Marrero MB, Venema VJ, Ju H, He H, Liang H, Caldwell RB, et al. (October 1999). "Endothelial nitric oxide synthase interactions with G-protein-coupled receptors". The Biochemical Journal. 343 Pt 2 (Pt 2): 335–340. doi:10.1042/0264-6021:3430335. PMC 1220558. PMID 10510297.
• Reyes-Cruz G, Vázquez-Prado J, Müller-Esterl W, Vaca L (January 2000). "Regulation of the human bradykinin B2 receptor expressed in sf21 insect cells: a possible role for tyrosine kinases". Journal of Cellular Biochemistry. 76 (4): 658–673. doi:10.1002/(SICI)1097-4644(20000315)76:4<658::AID-JCB14>3.0.CO;2-7. PMID 10653985. S2CID 30042149.
• Golser R, Gorren AC, Leber A, Andrew P, Habisch HJ, Werner ER, et al. (February 2000). "Interaction of endothelial and neuronal nitric-oxide synthases with the bradykinin B2 receptor. Binding of an inhibitory peptide to the oxygenase domain blocks uncoupled NADPH oxidation". The Journal of Biological Chemistry. 275 (8): 5291–5296. doi:10.1074/jbc.275.8.5291. PMID 10681501.{{cite journal}}: CS1 maint: overridden setting (link)

External links

• "Bradykinin Receptors: B₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
• Human BDKRB2 genome location and BDKRB2 gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.