RAMP2

Summary

Gene Symbol: RAMP2
Description: receptor activity modifying protein 2
Alias: receptor activity-modifying protein 2, CRLR activity-modifying protein 2, calcitonin receptor-like receptor activity modifying protein 2, receptor (G protein-coupled) activity modifying protein 2, receptor (calcitonin) activity modifying protein 2
Species: human
Products:     RAMP2

Top Publications

  1. Kusano S, Kukimoto Niino M, Hino N, Ohsawa N, Okuda K, Sakamoto K, et al. Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. 2012;21:199-210 pubmed publisher
    ..receptor-like receptor (CRLR), a class B GPCR, forms a heterodimer with receptor activity-modifying protein 2 (RAMP2), and serves as the adrenomedullin (AM) receptor to control neovascularization, while CRLR and RAMP1 form the ..
  2. Kuwasako K, Shimekake Y, Masuda M, Nakahara K, Yoshida T, Kitaura M, et al. Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling. J Biol Chem. 2000;275:29602-9 pubmed
    ..can produce calcitonin gene-related peptide (CGRP) receptors (CRLR/RAMP1) and adrenomedullin (AM) receptors (CRLR/RAMP2 or -3)...
  3. Qi T, Christopoulos G, Bailey R, Christopoulos A, Sexton P, Hay D. Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function. Mol Pharmacol. 2008;74:1059-71 pubmed publisher
    ..Calcitonin gene-related peptide (CGRP) receptors are CL/RAMP1, whereas adrenomedullin (AM) receptors are CL/RAMP2 (AM1 receptor) or CL/RAMP3 (AM2 receptor)...
  4. Ichikawa Shindo Y, Sakurai T, Kamiyoshi A, Kawate H, Iinuma N, Yoshizawa T, et al. The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity. J Clin Invest. 2008;118:29-39 pubmed
    ..The high-affinity AM receptor is composed of receptor activity-modifying protein 2 or 3 (RAMP2 or -3) and the GPCR calcitonin receptor-like receptor...
  5. McLatchie L, Fraser N, Main M, Wise A, Brown J, Thompson N, et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature. 1998;393:333-9 pubmed
    ..RAMP1 presents the receptor at the cell surface as a mature glycoprotein and a CGRP receptor. RAMP2-transported receptors are core-glycosylated and are adrenomedullin receptors.
  6. Bell D, Zhao Y, Devine A, McDermott B. Influence of atenolol and nifedipine on nitric-oxide deficient cardiomyocyte hypertrophy and expression of the cardio-endocrine peptide intermedin and its receptor components. Cell Physiol Biochem. 2008;21:203-14 pubmed publisher
    ..genes; (ii) normalized augmented membrane protein oxidation; (iii) normalized mRNA expression of AM, IMD, RAMP1, RAMP2 and RAMP3...
  7. Iesato Y. [Adrenomedullin-Receptor Activity-modifying Protein 2 (RAMP2) System in Retinal Angiogenesis]. Nippon Ganka Gakkai Zasshi. 2015;119:761-71 pubmed
    ..The vascular function of ADM is mainly regulated by a receptor activity-modifying protein 2 (RAMP2). However, pathophysiological roles of ADM-RAMP2 system in retinal angiogenesis remain to be clarified...
  8. Barbash S, Persson T, Lorenzen E, Kazmi M, Huber T, Sakmar T. Detection of Concordance between Transcriptional Levels of GPCRs and Receptor-Activity-Modifying Proteins. iScience. 2019;11:366-374 pubmed publisher
    ..As a proof-of-concept experiment, we over-expressed RAMP2 in HEK293T cells and evaluated the effect on the transcriptional levels of 14 representative GPCRs that were ..
  9. Chauhan M, Balakrishnan M, Vidaeff A, Yallampalli U, Lugo F, Fox K, et al. Adrenomedullin2 (ADM2)/Intermedin (IMD): A Potential Role in the Pathophysiology of Preeclampsia. J Clin Endocrinol Metab. 2016;101:4478-4488 pubmed

More Information

Publications100

  1. Shindo T, Tanaka M, Kamiyoshi A, Ichikawa Shindo Y, Kawate H, Yamauchi A, et al. Regulation of cardiovascular development and homeostasis by the adrenomedullin-RAMP system. Peptides. 2019;111:55-61 pubmed publisher
    ..We found that phenotypes similar to AM-/- were reproduced only in RAMP2-/- mice...
  2. Mackie D, Al Mutairi F, Davis R, Kechele D, Nielsen N, Snyder J, et al. hCALCRL mutation causes autosomal recessive nonimmune hydrops fetalis with lymphatic dysplasia. J Exp Med. 2018;215:2339-2353 pubmed publisher
    ..Using three independent genetic mouse models we establish that the adrenomedullin-CLR-RAMP2 axis is both necessary and sufficient for driving lymphatic vascular proliferation...
  3. Hirabayashi K, Tanaka M, Imai A, Toriyama Y, Iesato Y, Sakurai T, et al. Development of a Novel Model of Central Retinal Vascular Occlusion and the Therapeutic Potential of the Adrenomedullin-Receptor Activity-Modifying Protein 2 System. Am J Pathol. 2019;189:449-466 pubmed publisher
    ..potential of the pleiotropic peptide adrenomedullin (ADM) and its receptor activity-modifying protein 2 (RAMP2). The CRVO model, which had phenotypes resembling those seen in the clinic, was produced by combining i.p...
  4. Igarashi K, Sakurai T, Kamiyoshi A, Ichikawa Shindo Y, Kawate H, Yamauchi A, et al. Pathophysiological roles of adrenomedullin-RAMP2 system in acute and chronic cerebral ischemia. Peptides. 2014;62:21-31 pubmed publisher
    The accessory protein RAMP2 is a component of the CLR/RAMP2 dimeric adrenomedullin (AM) receptor and is the primary determinant of the vascular functionality of AM...
  5. Qiao X, Wang L, Wang Y, Zhao N, Zhang R, Han W, et al. Intermedin is upregulated and attenuates renal fibrosis by inhibition of oxidative stress in rats with unilateral ureteral obstruction. Nephrology (Carlton). 2015;20:820-31 pubmed publisher
    ..mRNA and protein expression of IMD increased after UUO. CRLR, RAMP1, RAMP2 and RAMP3 were also induced by ureteral obstruction...
  6. Roehrkasse A, Booe J, Lee S, Warner M, Pioszak A. Structure-function analyses reveal a triple β-turn receptor-bound conformation of adrenomedullin 2/intermedin and enable peptide antagonist design. J Biol Chem. 2018;293:15840-15854 pubmed publisher
    ..The CGRP receptor (RAMP1:CLR) favors CGRP binding, whereas the AM1 (RAMP2:CLR) and AM2 (RAMP3:CLR) receptors favor AM binding...
  7. Schönauer R, Kaiser A, Holze C, Babilon S, Köbberling J, Riedl B, et al. Fluorescently labeled adrenomedullin allows real-time monitoring of adrenomedullin receptor trafficking in living cells. J Pept Sci. 2015;21:905-12 pubmed publisher
    ..receptor (CLR), a G protein-coupled receptor, associated with the receptor activity-modifying protein 2 (RAMP2)...
  8. Benyahia Z, Dussault N, Cayol M, Sigaud R, Berenguer Daize C, Delfino C, et al. Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion. Oncotarget. 2017;8:15744-15762 pubmed publisher
    ..growth through its receptors calcitonin receptor-like receptor/receptor activity modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3)...
  9. Yamauchi A, Sakurai T, Kamiyoshi A, Ichikawa Shindo Y, Kawate H, Igarashi K, et al. Functional differentiation of RAMP2 and RAMP3 in their regulation of the vascular system. J Mol Cell Cardiol. 2014;77:73-85 pubmed publisher
    ..AM receptors are dimers consisting of CLR with one of two accessory proteins, RAMP2 or RAMP3...
  10. Tsuruda T, Kato J, Kuwasako K, Kitamura K. Adrenomedullin: Continuing to explore cardioprotection. Peptides. 2019;111:47-54 pubmed publisher
    ..calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein (RAMP) 2 or 3, and the AM-CLR/RAMP2 system is essential for heart development during embryogenesis...
  11. Hatzirodos N, Hummitzsch K, Irving Rodgers H, Rodgers R. Transcriptome comparisons identify new cell markers for theca interna and granulosa cells from small and large antral ovarian follicles. PLoS ONE. 2015;10:e0119800 pubmed publisher
    ..APOD, COL5A2, IGF2, NID1, LHFP, ACTA2, DUSP12, ACTG2, SPARCL1, FILIP1L, EGFLAM, ADAMDEC1, HPGD, COL12A1, FBLN5, RAMP2, COL15A1, PLK2, COL6A3, LOXL1, RARRES1, FLI1, LAMA2). Many of these were stromal extracellular matrix genes...
  12. Shindo T, Sakurai T, Kamiyoshi A, Ichikawa Shindo Y, Shimoyama N, Iinuma N, et al. Regulation of adrenomedullin and its family peptide by RAMP system--lessons from genetically engineered mice. Curr Protein Pept Sci. 2013;14:347-57 pubmed
    ..By interacting with RAMP1, CLR exhibits a high affinity for CGRP, whereas by interacting with either RAMP2 or -3, CLR exhibits a high affinity for ADM...
  13. Simms J, Routledge S, Uddin R, Poyner D. The Structure of the CGRP and Related Receptors. Handb Exp Pharmacol. 2018;: pubmed publisher
    ..Comparison with the crystal structure of a fragment of the allied peptide adrenomedullin bound to the ECD of CLR/RAMP2 confirms the importance of the interaction of the ligand C-terminus and the RAMP in determining pharmacology ..
  14. Chauhan M, Yallampalli U, Banadakappa M, Yallampalli C. Involvement of Receptor Activity-Modifying Protein 3 (RAMP3) in the Vascular Actions of Adrenomedullin in Rat Mesenteric Artery Smooth Muscle Cells. Biol Reprod. 2015;93:116 pubmed publisher
    ..Knockdown of RAMP2 was ineffective, whereas knockdown of RAMP3 inhibited ADM-induced cAMP production in VSMCs, suggesting involvement ..
  15. Kusano S, Yokoyama S. Ectodomain structures of the CGRP and AM receptors. Curr Protein Pept Sci. 2013;14:375-85 pubmed
    ..CLR•RAMP1 heterodimer functions mainly as the calcitonin gene-related peptide (CGRP) receptor, while the CLR•RAMP2 and CLR•RAMP3 heterodimers primarily function as the adrenomedullin 1 and adrenomedullin 2 (AM? and AM?) ..
  16. Lee S, Hay D, Pioszak A. Calcitonin and Amylin Receptor Peptide Interaction Mechanisms: INSIGHTS INTO PEPTIDE-BINDING MODES AND ALLOSTERIC MODULATION OF THE CALCITONIN RECEPTOR BY RECEPTOR ACTIVITY-MODIFYING PROTEINS. J Biol Chem. 2016;291:8686-700 pubmed publisher
    ..RAMP1/2 alter CLR selectivity for CGRP/AM in part by RAMP1 Trp-84 or RAMP2 Glu-101 contacting the distinct CGRP/AM C-terminal residues...
  17. Yoshimoto Y, Nishie T, Ito S, Kobayashi Y, Yamamoto Y, Okuda K, et al. Adrenomedullin regulates the speed of oviductal fluid flow in cattle. Mol Reprod Dev. 2017;84:712-718 pubmed publisher
    ..First, we examined the expression of ADM, CRLR, RAMP2, and RAMP3 mRNAs in isolated epithelial cells throughout the estrous cycle, and the localization of ADM receptor ..
  18. Woolley M, Conner A. Comparing the molecular pharmacology of CGRP and adrenomedullin. Curr Protein Pept Sci. 2013;14:358-74 pubmed
    ..For CGRP this is receptor activity-modifying protein 1 [RAMP1] and for AM acting at the AM1 receptor this is RAMP2. Receptor signalling by two specific peptide ligands through a common GPCR provides researchers with vital and ..
  19. Takano S, Uchida K, Miyagi M, Inoue G, Aikawa J, Iwabuchi K, et al. Adrenomedullin Regulates IL-1? Gene Expression in F4/80+ Macrophages during Synovial Inflammation. J Immunol Res. 2017;2017:9832430 pubmed publisher
    ..Higher gene expression of CD11c, IL-1?, AM, receptor activity-modifying proteins 2 (RAMP2), and 3 (RAMP3) was also observed in ST obtained from the dislocated side...
  20. Kuwasako K, Hay D, Nagata S, Murakami M, Kitamura K, Kato J. Functions of third extracellular loop and helix 8 of Family B GPCRs complexed with RAMPs and characteristics of their receptor trafficking. Curr Protein Pept Sci. 2013;14:416-28 pubmed
    At least one of three receptor activity-modifying proteins (RAMP1, RAMP2 and RAMP3) can interact with 10 G protein-coupled receptors (GPCRs; nine Family B GPCRs and a Family C GPCR)...
  21. Dong Y, Betancourt A, Belfort M, Yallampalli C. Targeting Adrenomedullin to Improve Lipid Homeostasis in Diabetic Pregnancies. J Clin Endocrinol Metab. 2017;102:3425-3436 pubmed publisher
    ..To our knowledge, manipulation of AM and its receptors in adipocytes might represent an approach in reducing the risk of GDM and fetal overgrowth. ..
  22. Greillier L, Tounsi A, Berenguer Daizé C, Dussault N, Delfino C, Benyahia Z, et al. Functional Analysis of the Adrenomedullin Pathway in Malignant Pleural Mesothelioma. J Thorac Oncol. 2016;11:94-107 pubmed publisher
    ..after binding to its receptors, calcitonin receptor-like receptor/receptor activity-modifying protein 2 (CLR/RAMP2) and calcitonin receptor-like receptor/receptor activity-modifying protein 3 (CLR/RAMP3)...
  23. Csont T, Murlasits Z, Ménesi D, Kelemen J, Bencsik P, Pipicz M, et al. Tissue-specific Gene Expression in Rat Hearts and Aortas in a Model of Vascular Nitrate Tolerance. J Cardiovasc Pharmacol. 2015;65:485-93 pubmed publisher
    ..altered in the aorta (increased: Tas2r119, Ihh, Rrad, Npm1, Snai1; decreased: Tubb2b, Usp15, Sema6c, Wfdc2, Rps21, Ramp2, Galr1, Atxn1, Lhx1) in vascular nitrate tolerance...
  24. Fernández A, Masa J, Guedan M, Futch H, Martínez Murillo R. Adrenomedullin Expression in Alzheimer's Brain. Curr Alzheimer Res. 2016;13:428-38 pubmed
    ..AM upregulation contributes to neuroprotection, but understanding the precise roles played by AM and its receptor (RAMP2) in neurodegenerative diseases including Alzheimer's disease (AD), awaits further research...
  25. Booe J, Warner M, Roehrkasse A, Hay D, Pioszak A. Probing the Mechanism of Receptor Activity-Modifying Protein Modulation of GPCR Ligand Selectivity through Rational Design of Potent Adrenomedullin and Calcitonin Gene-Related Peptide Antagonists. Mol Pharmacol. 2018;93:355-367 pubmed publisher
    ..RAMP1 favors CGRP, whereas RAMP2 and RAMP3 favor AM...
  26. Figueira L, Israel A. Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation During Hypertension. Cerebellum. 2017;16:132-141 pubmed publisher
    ..receptors components, calcitonin-receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP1, RAMP2, and RAMP3) are expressed in cerebellum...
  27. Sogbe Díaz M, Díaz López E. [Adrenomedullin in the kidney: physiology and pathophysiology]. Invest Clin. 2016;57:66-76 pubmed
    ..composed of the calcitonin-receptor-like receptor (CLR) and one of two receptor activity modifying proteins (RAMP2 or RAMP3). The CLR/RAMP2 (AM1 receptor) is more highly AM-specific than The CLR/RAMP3 (AM2 receptor)...
  28. Tanaka M, Koyama T, Sakurai T, Kamiyoshi A, Ichikawa Shindo Y, Kawate H, et al. The endothelial adrenomedullin-RAMP2 system regulates vascular integrity and suppresses tumour metastasis. Cardiovasc Res. 2016;111:398-409 pubmed publisher
    ..Adrenomedullin (AM) and its receptor-modulating protein, RAMP2, have been identified as essential mediators of cardiovascular homeostasis...
  29. Sun P, Zhu K, Wang C, Liu W, Peng D, Zhao X. Prophylactic effects of alkaloids from Ba lotus seeds on L-NNA-induced hypertension in mice. Chin J Nat Med. 2016;14:835-843 pubmed publisher
    ..The ABLS treated mice had higher mRNA expressions of HO-1, nNOS, and eNOS and lower expressions of ADM, RAMP2, IL-1?, TNF-?, and iNOS than the control mice...
  30. Meng Q, Shi D, Feng J, Su Y, Long Y, He S, et al. Hypercholesterolemia Up-Regulates the Expression of Intermedin and Its Receptor Components in the Aorta of Rats via Inducing the Oxidative Stress. Ann Clin Lab Sci. 2016;46:5-17 pubmed
    ..Increased expression of IMD and all its receptor components (CRLR, RAMP1, RAMP2, and RAMP3) were displayed within the aorta...
  31. Figueira L, Israel A. Role of cerebellar adrenomedullin in blood pressure regulation. Neuropeptides. 2015;54:59-66 pubmed publisher
    ..To further evaluate the role of AM in cerebellum, we assessed the expression of AM, RAMP1, RAMP2, RAMP3 and CRLR in the cerebellar vermis of 8 and 16week old spontaneously hypertensive (SHR) and normotensive ..
  32. Kato J, Kitamura K. Bench-to-bedside pharmacology of adrenomedullin. Eur J Pharmacol. 2015;764:140-8 pubmed publisher
    ..Taking these findings together, AM is a bioactive peptide with pleiotropic effects, with potential as a therapeutic tool for a wide range of human diseases from myocardial infarction to malignant tumors or inflammatory bowel diseases. ..
  33. Castellani G, Paliuri G, Orso G, Paccagnella N, D Amore C, Facci L, et al. An intracellular adrenomedullin system reduces IL-6 release via a NF-kB-mediated, cAMP-independent transcriptional mechanism in rat thymic epithelial cells. Cytokine. 2016;88:136-143 pubmed publisher
    ..In a previous paper we reported that adrenomedullin (ADM) and its co-receptor protein RAMP2 are located intracellularly in newborn human thymic epithelial cells (TECs)...
  34. Xian X, Sakurai T, Kamiyoshi A, Ichikawa Shindo Y, Tanaka M, Koyama T, et al. Vasoprotective Activities of the Adrenomedullin-RAMP2 System in Endothelial Cells. Endocrinology. 2017;158:1359-1372 pubmed publisher
    ..In the present study, we assessed the vasoprotective actions of the endogenous AM-RAMP2 system using a wire-induced vascular injury model...
  35. Dong N, Meng L, Xue R, Yu M, Zhao Z, Liu X. Adrenomedullin ameliorates podocyte injury induced by puromycin aminonucleoside in vitro and in vivo through modulation of Rho GTPases. Int Urol Nephrol. 2017;49:1489-1506 pubmed publisher
    ..PAN increased the expressions of endogenous AM and its receptor RAMP2 which was furthermore upregulated by AM administration...
  36. Chauhan M, Betancourt A, Balakrishnan M, Yallampalli U, Dong Y, Fox K, et al. Impaired Vasodilatory Responses of Omental Arteries to CGRP Family Peptides in Pregnancies Complicated by Fetal Growth Restriction. J Clin Endocrinol Metab. 2016;101:2984-93 pubmed publisher
    ..was lower in OA from FGR pregnancy compared to the normal, and 5) mRNA and protein levels of RAMP1, RAMP2, and RAMP3 were lower in OA isolated from FGR pregnancies compared to the normal...
  37. Bell D, Campbell M, McAleer S, Ferguson M, Donaghy L, Harbinson M. Endothelium-derived intermedin/adrenomedullin-2 protects human ventricular cardiomyocytes from ischaemia-reoxygenation injury predominantly via the AM₁ receptor. Peptides. 2016;76:1-13 pubmed publisher
    ..Pre-treatment (4 days) of HCM with CLR and RAMP2 siRNAs attenuated (P<0.05) protection by exogenous IMD...
  38. Figueira L, Israel A. Cerebellar Adrenomedullinergic System. Role in Cardiovascular Regulation. Adv Exp Med Biol. 2017;956:541-560 pubmed publisher
    ..is a multifunctional peptide which exerts numerous biological activities through the activation of AM1 (CRLR?+ RAMP2) and AM2 (CRLR?+?RAMP3) receptors...
  39. Xu M, Qi F, Zhang S, Ma X, Wang S, Wang C, et al. Adrenomedullin promotes the growth of pancreatic ductal adenocarcinoma through recruitment of myelomonocytic cells. Oncotarget. 2016;7:55043-55056 pubmed publisher
    ..ADM), and CD11b+ myelomonocytic cells expressed all components of ADM receptors, including GPR182, CRLR, RAMP2 and RAMP3...
  40. Kach J, Sandbo N, Sethakorn N, Williams J, Reed E, La J, et al. Regulation of myofibroblast differentiation and bleomycin-induced pulmonary fibrosis by adrenomedullin. Am J Physiol Lung Cell Mol Physiol. 2013;304:L757-64 pubmed publisher
    ..Finally, sensitization of ADM signaling by transgenic overexpression of RAMP2 in myofibroblasts resulted in enhanced survival and reduced pulmonary fibrosis in the bleomycin model of the ..
  41. Kuwasako K, Sekiguchi T, Nagata S, Jiang D, Hayashi H, Murakami M, et al. Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor. Biochem Biophys Res Commun. 2016;470:894-9 pubmed publisher
    Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor-like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM1 receptor)...
  42. Koyama T, Sakurai T, Kamiyoshi A, Ichikawa Shindo Y, Kawate H, Shindo T. Adrenomedullin-RAMP2 System in Vascular Endothelial Cells. J Atheroscler Thromb. 2015;22:647-53 pubmed publisher
    ..We have reported that knockout mice deficient in AM or receptor activity-modifying protein 2 (RAMP2), an AM-receptor accessory protein, show vascular endothelial cell deformities that are embryonically lethal...
  43. van Son M, Tremoen N, Gaustad A, Myromslien F, Våge D, Stenseth E, et al. RNA sequencing reveals candidate genes and polymorphisms related to sperm DNA integrity in testis tissue from boars. BMC Vet Res. 2017;13:362 pubmed publisher
    ..Validation showed that predicted high impact variants in RAMP2, GIMAP6 and three uncharacterized genes are particularly interesting for sperm DNA fragmentation in boars...
  44. Hay D, Walker C, Gingell J, Ladds G, Reynolds C, Poyner D. Receptor activity-modifying proteins; multifunctional G protein-coupled receptor accessory proteins. Biochem Soc Trans. 2016;44:568-73 pubmed publisher
    ..developments on the structure of the complexes formed between the extracellular domains (ECDs) of CLR and RAMP1 or RAMP2 as these provide insights as to how the RAMPs direct ligand binding...
  45. Uetake R, Sakurai T, Kamiyoshi A, Ichikawa Shindo Y, Kawate H, Iesato Y, et al. Adrenomedullin-RAMP2 system suppresses ER stress-induced tubule cell death and is involved in kidney protection. PLoS ONE. 2014;9:e87667 pubmed publisher
    ..Among the RAMP subisoforms, only RAMP2 knockout mice ?/? reproduce the phenotype of embryonic lethality of AM?/?, illustrating the importance of the AM-..
  46. Yamauchi A, Kamiyoshi A, Koyama T, Iinuma N, Yamaguchi S, Miyazaki H, et al. Placental extract ameliorates non-alcoholic steatohepatitis (NASH) by exerting protective effects on endothelial cells. Heliyon. 2017;3:e00416 pubmed publisher
    ..MCD diet with high-salt loading (8% NaCl in the drinking water) to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE...
  47. Weston C, Lu J, Li N, Barkan K, Richards G, Roberts D, et al. Modulation of Glucagon Receptor Pharmacology by Receptor Activity-modifying Protein-2 (RAMP2). J Biol Chem. 2015;290:23009-22 pubmed publisher
    ..of multiple ligands, association with the receptor-interacting protein receptor activity-modifying protein-2 (RAMP2), and the role of individual G protein α-subunits...
  48. Derst C, Engel H, Grzeschik K, Daut J. Genomic structure and chromosome mapping of human and mouse RAMP genes. Cytogenet Cell Genet. 2000;90:115-8 pubmed
    ..The human RAMP1 and RAMP3 genes possess two introns and human RAMP2 possesses three introns. Human RAMP1 was assigned to chromosome 2q36-->q37.1, RAMP2 to 17q12-->q21...
  49. Udawela M, Christopoulos G, Morfis M, Christopoulos A, Ye S, Tilakaratne N, et al. A critical role for the short intracellular C terminus in receptor activity-modifying protein function. Mol Pharmacol. 2006;70:1750-60 pubmed
    ..Thus, this study reveals important functionality of the RAMP C-terminal domain and identifies key differences in the role of the RAMP C terminus for CTR versus CLR-based receptors. ..
  50. Hay D, Garelja M, Poyner D, Walker C. Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review:"X". Br J Pharmacol. 2017;: pubmed publisher
    ..This gives the CGRP receptor (CLR/RAMP1), the AM1 and AM2 receptors (CLR/RAMP2 or RAMP3) and the AMY1, AMY2 and AMY3 receptors (CTR/RAMPs1-3 complexes, ..
  51. Aiyar N, Disa J, Ao Z, Xu D, Surya A, Pillarisetti K, et al. Molecular cloning and pharmacological characterization of bovine calcitonin receptor-like receptor from bovine aortic endothelial cells. Biochem Pharmacol. 2002;63:1949-59 pubmed
    ..Co-transfection of bovine CRLR with human RAMP2 or RAMP3 cDNAs in HEK-293 cells displayed high-affinity ADM receptors...
  52. Cegla J, Jones B, Gardiner J, Hodson D, Marjot T, McGlone E, et al. RAMP2 Influences Glucagon Receptor Pharmacology via Trafficking and Signaling. Endocrinology. 2017;158:2680-2693 pubmed publisher
    ..and Gαq pathways and β-arrestin recruitment, and small interfering RNA knockdown to examine the effect of RAMP2 on the GCGR...
  53. Albertin G, Ruggero M, Guidolin D, Nussdorfer G. Gene silencing of human RAMP2 mediated by short-interfering RNA. Int J Mol Med. 2006;18:531-5 pubmed
    ..of the calcitonin receptor-like receptors with two chaperones, called receptor activity modifying proteins (RAMP2 and RAMP3)...
  54. Qing X, Svaren J, Keith I. mRNA expression of novel CGRP1 receptors and their activity-modifying proteins in hypoxic rat lung. Am J Physiol Lung Cell Mol Physiol. 2001;280:L547-54 pubmed
    ..specificity of CRLR: coexpression of CRLR and RAMP1 results in a CGRP1 receptor, whereas coexpression of CRLR and RAMP2 or -3 results in an ADM receptor...
  55. Watkins H, Chakravarthy M, Abhayawardana R, Gingell J, Garelja M, Pardamwar M, et al. Receptor Activity-modifying Proteins 2 and 3 Generate Adrenomedullin Receptor Subtypes with Distinct Molecular Properties. J Biol Chem. 2016;291:11657-75 pubmed publisher
    ..receptor, the calcitonin receptor-like receptor (CLR), and receptor activity-modifying proteins 2 and 3 (RAMP2 and RAMP3), respectively...
  56. Kadmiel M, Matson B, Espenschied S, Lenhart P, Caron K. Loss of receptor activity-modifying protein 2 in mice causes placental dysfunction and alters PTH1R regulation. PLoS ONE. 2017;12:e0181597 pubmed publisher
    Receptor activity-modifying protein 2 (Ramp2) is a single-pass transmembrane protein that heterodimerizes with several family B G-protein coupled receptors to alter their function...
  57. Udawela M, Christopoulos G, Tilakaratne N, Christopoulos A, Albiston A, Sexton P. Distinct receptor activity-modifying protein domains differentially modulate interaction with calcitonin receptors. Mol Pharmacol. 2006;69:1984-9 pubmed
    ..We have used chimeras between RAMP1 and RAMP2 that specifically exchanged the N-terminal, transmembrane, or C-terminal domain and examined these in assays of [(..
  58. Kuwasako K, Cao Y, Nagoshi Y, Tsuruda T, Kitamura K, Eto T. Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins. Mol Pharmacol. 2004;65:207-13 pubmed
    ..By contrast, [Tyr0]hCGRPalpha binding and signaling were markedly weaker with CTR2/RAMP2 or -3 than with CTR2/RAMP1 or CRLR/RAMP1; likewise, 125I-[His10]hCGRPalpha bound most potently to CTR2/RAMP1...
  59. Yue W, Dacic S, Sun Q, Landreneau R, Guo M, Zhou W, et al. Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation. Clin Cancer Res. 2007;13:4336-44 pubmed
    ..and functional analyses were done to study the role of one candidate gene, receptor activity-modifying protein 2 (RAMP2), in suppressing lung cancer cell growth...
  60. Hilairet S, Foord S, Marshall F, Bouvier M. Protein-protein interaction and not glycosylation determines the binding selectivity of heterodimers between the calcitonin receptor-like receptor and the receptor activity-modifying proteins. J Biol Chem. 2001;276:29575-81 pubmed
    ..In contrast, RAMP2 and -3 promoted the expression of smaller, core-glycosylated, CRLR forms, which were linked to AM receptor ..
  61. Ramos C, Sun X, Johnson E, Nelson H, Gonzalez Bosc L. Adrenomedullin expression in the developing human fetal lung. J Investig Med. 2014;62:49-55 pubmed publisher
    ..The gene expression of AM, CRLR, RAMP2, and RAMP3 was measured with real-time reverse-transcription polymerase chain reaction...
  62. Kuwasako K, Cao Y, Chu C, Iwatsubo S, Eto T, Kitamura K. Functions of the cytoplasmic tails of the human receptor activity-modifying protein components of calcitonin gene-related peptide and adrenomedullin receptors. J Biol Chem. 2006;281:7205-13 pubmed
    ..to function as a calcitonin gene-related peptide receptor (CRLR/RAMP1) or an adrenomedullin (AM) receptor (CRLR/RAMP2 or -3)...
  63. Pawlak J, Wetzel Strong S, Dunn M, Caron K. Cardiovascular effects of exogenous adrenomedullin and CGRP in Ramp and Calcrl deficient mice. Peptides. 2017;88:1-7 pubmed publisher
    ..the ligand binding affinity of the receptor such that the CLR/RAMP1 heterodimer preferably binds CGRP, while CLR/RAMP2 and CLR/RAMP3 have a stronger affinity for AM...
  64. De Martin S, Paliuri G, Belloni A, Orso G, Zanarella E, Stellin G, et al. Expression and distribution of the adrenomedullin system in newborn human thymus. PLoS ONE. 2014;9:e97592 pubmed publisher
    ..the calcitonin receptor-like receptor (CLR), which couples to the receptor activity-modifying proteins 2 or 3 (RAMP2 or RAMP3) to form the functional plasma membrane receptors AM1 and AM2, respectively...
  65. Koyama T, Kuriyama N, Ozaki E, Matsui D, Watanabe I, Takeshita W, et al. Genetic Variants of RAMP2 and CLR are Associated with Stroke. J Atheroscler Thromb. 2017;24:1267-1281 pubmed publisher
    ..We analyzed single nucleotide polymorphisms (SNPs) in the RAMP2 and CLR genes to determine their association with stroke in the light of gene-environment interactions.
  66. Kuwasako K, Kitamura K, Ito K, Uemura T, Yanagita Y, Kato J, et al. The seven amino acids of human RAMP2 (86) and RAMP3 (59) are critical for agonist binding to human adrenomedullin receptors. J Biol Chem. 2001;276:49459-65 pubmed
    ..can function as a calcitonin gene-related peptide receptor (CRLR-RAMP1) or an adrenomedullin (AM) receptor (CRLR-RAMP2/3)...
  67. Menon R, Shrestha A, Shivanna B. Hyperoxia exposure disrupts adrenomedullin signaling in newborn mice: Implications for lung development in premature infants. Biochem Biophys Res Commun. 2017;487:666-671 pubmed publisher
    ..via its cognate receptors, calcitonin receptor-like receptor (Calcrl) and receptor activity-modifying protein 2 (RAMP2)...
  68. Kuwasako K, Kitamura K, Nagoshi Y, Eto T. Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from co-expression of calcitonin receptor with receptor activity-modifying proteins. Biochem Biophys Res Commun. 2003;301:460-4 pubmed
    ..Co-expression of CTR(I1-) with RAMP thus appears to produce functional CT-(8-32)-sensitive AM receptors. ..
  69. Lee S, Booe J, Gingell J, Sjoelund V, Hay D, Pioszak A. N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity. Biochemistry. 2017;56:3380-3393 pubmed publisher
    ..Similar results were observed for an amylin receptor RAMP2-CTR ECD complex...
  70. Dumont C, Muff R, Fluhmann B, Fischer J, Born W. Paracrine/autocrine function of adrenomedullin in peripheral nerves of rats. Brain Res. 2002;955:64-71 pubmed
    ..all the primary cells, but the levels of RAMP1 mRNA relative to 18s rRNA were 10-fold lower than those of CRLR and RAMP2 and -3 encoding mRNA...
  71. Dong Y, Chauhan M, Belfort M, Yallampalli C. Calcitonin Gene-Related Peptide Rescues Proximity Associations of Its Receptor Components, Calcitonin Receptor-Like Receptor and Receptor Activity-Modifying Protein 1, in Rat Uterine Artery Smooth Muscle Cells Exposed to Tumor Necrosis Factor Alpha. Biol Reprod. 2016;95:126 pubmed
    ..this study shows that CALCRL predominantly associates with RAMP1 forming a CALCB receptor, and minimally with RAMP2 and RAMP3 that confer specificity for ADM and ADM2...
  72. Wang Y, Zhang J, Li J, Lan L, Yang Z, Wang S. [Increased atria expression of receptor activity-modifying proteins in heart failure patients]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004;21:351-4 pubmed
    ..of RAMP1 and CRLR results in a calcitonin gene related peptide (CGRP) receptor, whereas the association of RAMP2 or RAMP3 with CRLR gives an adrenomedullin(ADM) receptor...
  73. Aldecoa A, Gujer R, Fischer J, Born W. Mammalian calcitonin receptor-like receptor/receptor activity modifying protein complexes define calcitonin gene-related peptide and adrenomedullin receptors in Drosophila Schneider 2 cells. FEBS Lett. 2000;471:156-60 pubmed
    ..from mammalian cells, rCRLR expressed in S2 cells are uniformly glycosylated proteins independent of RAMP1 or RAMP2. Bis(sulfosuccinimidyl)suberate cross-linking revealed receptor components with the size of rCRLR, increased by ..
  74. Fu W, Ruangkittisakul A, MacTavish D, Shi J, Ballanyi K, Jhamandas J. Amyloid ? (A?) peptide directly activates amylin-3 receptor subtype by triggering multiple intracellular signaling pathways. J Biol Chem. 2012;287:18820-30 pubmed publisher
  75. Albertin G, Sorato E, Oselladore B, Mascarin A, Tortorella C, Guidolin D. Involvement of vascular endothelial growth factor signaling in CLR/RAMP1 and CLR/RAMP2-mediated pro-angiogenic effect of intermedin on human vascular endothelial cells. Int J Mol Med. 2010;26:289-94 pubmed
    ..Real-time PCR demonstrated the expression of IMD, CLR/RAMP1 and CLR/RAMP2 (but not CLR/RAMP3) mRNA in HUVECs...
  76. Bomberger J, Parameswaran N, Hall C, Aiyar N, Spielman W. Novel function for receptor activity-modifying proteins (RAMPs) in post-endocytic receptor trafficking. J Biol Chem. 2005;280:9297-307 pubmed
    ..For example, adrenomedullin receptors are comprised of RAMP2 or RAMP3 (AM1R and AM2R, respectively) and calcitonin receptor-like receptor (CRLR), while a CRLR heterodimer with ..
  77. Foord S, Marshall F. RAMPs: accessory proteins for seven transmembrane domain receptors. Trends Pharmacol Sci. 1999;20:184-7 pubmed
  78. Prado M, Evans Bain B, Oliver K, Dickerson I. The role of the CGRP-receptor component protein (RCP) in adrenomedullin receptor signal transduction. Peptides. 2001;22:1773-81 pubmed
    ..adrenomedullin receptors when co-expressed with the accessory protein receptor-activity modifying protein 2 (RAMP2)...
  79. Kuwasako K, Kitamura K, Nagata S, Hikosaka T, Kato J. Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2. Biochem Biophys Res Commun. 2010;392:380-5 pubmed publisher
    Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor...
  80. Michou L, Garnier S, Barbet S, Glikmans E, Ea H, Uzan B, et al. Lack of linkage and association of adrenomedullin and its receptor genes in French Caucasian rheumatoid arthritis trio families. Clin Exp Rheumatol. 2008;26:1083-6 pubmed
    ..Our findings provided no significant linkage or association of adrenomedullin and CRLR-RAMP-2 genes with RA in the studied trio families. The two CRLR polymorphisms rs3771076 and rs3771084 should be investigated in larger samples. ..
  81. Kuwasako K, Kitamura K, Nagata S, Kato J. Functions of the extracellular histidine residues of receptor activity-modifying proteins vary within adrenomedullin receptors. Biochem Biophys Res Commun. 2008;377:109-13 pubmed publisher
    ..Other His residues appeared uninvolved in hCRLR-related functions. Thus, the His residues of hRAMP2 and -3 differentially govern AM receptor function. ..
  82. Christopoulos A, Christopoulos G, Morfis M, Udawela M, Laburthe M, Couvineau A, et al. Novel receptor partners and function of receptor activity-modifying proteins. J Biol Chem. 2003;278:3293-7 pubmed
    ..cyclase-activating peptide receptor with all three RAMPs; the glucagon and PTH1 parathyroid hormone receptors with RAMP2; and the PTH2 receptor with RAMP3...
  83. Kuwasako K, Kitamura K, Nagata S, Sekiguchi T, Danfeng J, Murakami M, et al. ?-arrestins negatively control human adrenomedullin type 1-receptor internalization. Biochem Biophys Res Commun. 2017;487:438-443 pubmed publisher
    ..which consists of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2)...
  84. Watkins H, Walker C, Ly K, Bailey R, Barwell J, Poyner D, et al. Receptor activity-modifying protein-dependent effects of mutations in the calcitonin receptor-like receptor: implications for adrenomedullin and calcitonin gene-related peptide pharmacology. Br J Pharmacol. 2014;171:772-88 pubmed publisher
    ..Guided by receptor models, we mutated residues in the N-terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions...
  85. Booe J, Walker C, Barwell J, Kuteyi G, Simms J, Jamaluddin M, et al. Structural Basis for Receptor Activity-Modifying Protein-Dependent Selective Peptide Recognition by a G Protein-Coupled Receptor. Mol Cell. 2015;58:1040-52 pubmed publisher
    ..We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively...
  86. Nagoshi Y, Kuwasako K, Cao Y, Imamura T, Kitamura K, Eto T. Tumor necrosis factor-alpha downregulates adrenomedullin receptors in human coronary artery smooth muscle cells. Peptides. 2004;25:1115-21 pubmed
    ..comprised of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1) or RAMP2. TNF-alpha induced time- and dose-dependent decreases in the expression of CRLR and RAMP1/2 mRNAs, thereby ..
  87. Liu S, Mitra R, Zhao M, Fan W, Eischen C, Yin F, et al. The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development. Mol Cancer Ther. 2016;15:2977-2986 pubmed publisher
    ..Specifically, lncRNA RAMP2-AS1 had significant decrease of expression in glioblastoma tissues and showed coexpressional relationship with ..
  88. Roux B, Bauer C, McNeish A, Ward S, Cottrell G. The Role of Ubiquitination and Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate in the Degradation of the Adrenomedullin Type I Receptor. Sci Rep. 2017;7:12389 pubmed publisher
    Calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 2 (RAMP2) comprise a receptor for adrenomedullin (AM)...
  89. Oliver K, Wainwright A, Edvinsson L, Pickard J, Hill R. Immunohistochemical localization of calcitonin receptor-like receptor and receptor activity-modifying proteins in the human cerebral vasculature. J Cereb Blood Flow Metab. 2002;22:620-9 pubmed
    ..CRLR combined with RAMP binds calcitonin gene-related peptide with high affinity, whereas CRLR coexpression with RAMP2 or -3 confers high-affinity binding of adrenomedullin...
  90. Kechele D, Dunworth W, Trincot C, Wetzel Strong S, Li M, Ma H, et al. Endothelial Restoration of Receptor Activity-Modifying Protein 2 Is Sufficient to Rescue Lethality, but Survivors Develop Dilated Cardiomyopathy. Hypertension. 2016;68:667-77 pubmed publisher
    ..b>Ramp2 null mice are embryonic lethal, with cardiovascular developmental defects similar to those observed in mice null ..
  91. Kamitani S, Asakawa M, Shimekake Y, Kuwasako K, Nakahara K, Sakata T. The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells. FEBS Lett. 1999;448:111-4 pubmed
    ..Thus, the receptor activity-modifying protein 2/calcitonin receptor-like receptor complex apparently serves as a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells. ..