Affinage

RAMP2

Receptor activity-modifying protein 2 · UniProt O60895

Length
175 aa
Mass
19.6 kDa
Annotated
2026-04-28
44 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAMP2 is a single-pass transmembrane accessory protein that serves as an obligate co-receptor for the calcitonin receptor-like receptor (CLR/CRLR), forming the principal high-affinity adrenomedullin (AM) receptor (AM1 receptor) that signals through cAMP, and additionally functions as an allosteric modulator of multiple Family B GPCRs including the glucagon receptor (GCGR) and parathyroid hormone 1 receptor (PTH1R) (PMID:10217420, PMID:37001505, PMID:35914163). Seven N-terminal extracellular residues (86–92) are critical for AM binding specificity, and the RAMP2–CLR complex is pharmacologically distinct from the RAMP3–CLR (AM2) receptor (PMID:11591721, PMID:12970090). Through endothelial AM–RAMP2 signaling, RAMP2 maintains vascular integrity and barrier function by regulating the Rac1-GTP/RhoA-GTP balance, cortical actin organization, tight/adherens junction expression, and Epac1 levels; genetic ablation causes embryonic lethality with severe vascular fragility, and postnatal endothelial deletion leads to vascular hyperpermeability, organ fibrosis, accelerated senescence, and pre-metastatic niche formation (PMID:18097473, PMID:23355623, PMID:27307317, PMID:38012983). Pathogenic RAMP2 variants that disrupt AM–RAMP2/CRLR–cAMP signaling cause primary open-angle glaucoma (POAG), with mutant proteins aggregating intracellularly and heterozygous Ramp2 knockout mice exhibiting retinal ganglion cell death (PMID:31000793).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Established that RAMP2, when co-expressed with CRLR, constitutes a functional AM receptor that couples to cAMP — resolving how AM selectivity is determined at the receptor level.

    Evidence Co-expression in HeLa EBNA and HEK293 EBNA cells with cAMP measurement; RT-PCR for endogenous expression in ECs and VSMCs

    PMID:10217420

    Open questions at the time
    • Structural basis of RAMP2 vs RAMP1 selectivity for AM vs CGRP unknown
    • Endogenous stoichiometry and trafficking of the complex not examined
  2. 2001 High

    Identified a minimal seven-residue segment (86–92) in the RAMP2 N-terminal ectodomain as critical for AM binding and signaling, separating the ligand-recognition determinant from the receptor trafficking function.

    Evidence RAMP chimeras, deletion mutants, and alanine scanning co-expressed with CRLR in HEK293 cells; radioligand binding and cAMP assays with FACS surface-expression controls

    PMID:11591721

    Open questions at the time
    • No crystal or cryo-EM structure of AM–RAMP2–CLR to map contacts at atomic resolution
    • Contribution of CLR residues to AM selectivity not dissected
  3. 2003 High

    Demonstrated that CLR/RAMP2 and CLR/RAMP3 form pharmacologically distinct AM receptors with differing antagonist profiles, establishing the AM1/AM2 receptor nomenclature.

    Evidence Quantitative cAMP antagonism assays with pA2 calculations across Cos-7, Rat2, and L6 cells using AM22-52, CGRP8-37, and BIBN4096BS

    PMID:12970090

    Open questions at the time
    • Downstream signaling bias differences between AM1 and AM2 not characterized
    • Physiological contexts where AM2 substitutes for AM1 unclear
  4. 2008 High

    Revealed that RAMP2 is indispensable for vascular development and integrity in vivo — its complete loss causes midgestation lethality with vascular fragility, hemorrhage, and endothelial detachment, while haploinsufficiency impairs adult angiogenesis.

    Evidence RAMP2 knockout mice (lethal), heterozygous mice, and EC-specific RAMP2 overexpression; histology, immunofluorescence, permeability assays

    PMID:18097473

    Open questions at the time
    • Molecular pathway downstream of AM-RAMP2 mediating junction/basement-membrane gene expression not defined
    • Whether RAMP2 KO lethality is entirely AM-dependent or involves other CLR ligands unresolved
  5. 2013 High

    Defined the intracellular mechanism by which endothelial AM-RAMP2 maintains vascular barrier: control of the Rac1-GTP/RhoA-GTP balance and cortical actin organization; loss of this system triggers vascular leakage, fibrosis, and accelerated senescence.

    Evidence Endothelial-specific and drug-inducible endothelial RAMP2 KO mice; Rac1/RhoA activity assays; actin imaging; permeability measurements

    PMID:23355623

    Open questions at the time
    • Whether RAMP2 regulates Rac1/RhoA through Epac, PI3K, or another intermediate not resolved
    • Contribution of β-arrestin-dependent vs G-protein-dependent pathways to barrier function unknown
  6. 2013 High

    Extended the vascular role to retinal angiogenesis, showing RAMP2 haploinsufficiency reduces pathological neovascularization and VEGF/eNOS expression in oxygen-induced retinopathy.

    Evidence RAMP2+/− and DI-E-RAMP2−/− mice in OIR model; EC proliferation/migration assays; intravitreal anti-ADM antibody

    PMID:23562442

    Open questions at the time
    • Whether AM-RAMP2 directly transcribes VEGF or acts upstream via HIF not determined
    • Therapeutic window for targeting AM-RAMP2 in retinal disease undefined
  7. 2015 Medium

    Expanded RAMP2's receptor repertoire beyond CLR by showing it modulates glucagon receptor pharmacology — altering GCGR ligand selectivity and G-protein coupling preference.

    Evidence RAMP2-GCGR co-expression in yeast reporter and mammalian cell functional assays with multiple ligands

    PMID:26198634

    Open questions at the time
    • Direct physical interaction between RAMP2 and GCGR not confirmed by co-IP or structural data at this point
    • Physiological tissues where RAMP2-GCGR interaction occurs not identified
  8. 2017 Medium

    Showed RAMP2 causes intracellular redistribution of GCGR, reducing its surface expression and modulating both Gαs/Gαq signaling and β-arrestin recruitment — providing a trafficking-based mechanism for GCGR modulation.

    Evidence Confocal microscopy, cell-surface ELISA, competition binding, Gαs/Gαq assays, β-arrestin recruitment, siRNA knockdown

    PMID:28586439

    Open questions at the time
    • Whether RAMP2-induced GCGR internalization is constitutive or regulated not fully dissected
    • Structural interface between RAMP2 and GCGR undefined
  9. 2019 Medium

    Identified pathogenic RAMP2 variants as a cause of primary open-angle glaucoma (POAG), linking disrupted AM-RAMP2/CRLR-cAMP signaling and mutant protein aggregation to retinal ganglion cell death.

    Evidence Exome and Sanger sequencing of POAG families; transfection of mutant RAMP2; cAMP assays; RAMP2+/− mouse retinal histology

    PMID:31000793

    Open questions at the time
    • Number of POAG families carrying RAMP2 variants is small; replication in larger cohorts needed
    • Mechanism of mutant RAMP2 aggregation (misfolding vs ER retention) not characterized
  10. 2021 High

    Resolved the mechanism of RAMP2's GCGR modulation in hepatocytes: RAMP2 drives constitutive and agonist-stimulated GCGR internalization, biasing signaling toward endosomal Gαs/cAMP and away from β-arrestin-2, with long-term lysosomal degradation of GCGR.

    Evidence Confocal microscopy, radioligand binding, WASH-complex KO MEFs, monensin trafficking inhibition, NanoBiT complementation, cAMP assays, hepatocyte-targeted AAV in lean/obese mice

    PMID:34271220

    Open questions at the time
    • In vivo metabolic consequences of hepatic RAMP2-GCGR interaction in disease models not fully explored
    • Whether RAMP2-directed lysosomal degradation of GCGR is ubiquitin-dependent not tested
  11. 2021 High

    Demonstrated that cardiomyocyte AM-RAMP2 signaling maintains mitochondrial homeostasis under pressure overload, with cardiomyocyte-specific RAMP2 deletion causing cardiac hypertrophy, fibrosis, and impaired mitochondrial membrane potential and respiration.

    Evidence Cardiomyocyte-specific RAMP2 KO mice; TAC; echocardiography; PV loops; mitochondrial assays

    PMID:33545715

    Open questions at the time
    • Pathway linking AM-RAMP2-cAMP to mitochondrial biogenesis or quality control (e.g. PGC-1α, mitophagy) not identified
    • Whether cardiomyocyte RAMP2 also modulates other GPCRs in the heart not explored
  12. 2022 High

    Established that RAMP2 allosterically modulates PTH1R by shifting it to a preactivated conformation that accelerates activation and enhances Gi3 signaling and β-arrestin2 recruitment in a ligand-specific manner — broadening RAMP2's role to parathyroid hormone signaling.

    Evidence FRET/BRET biosensors for PTH1R conformational states and downstream signaling; RAMP2 co-expression; homology modelling

    PMID:35914163

    Open questions at the time
    • Structural basis of RAMP2-PTH1R interaction at atomic resolution not available
    • In vivo relevance to calcium/phosphate homeostasis or bone biology not tested
  13. 2023 High

    Provided the first near-atomic structural insight into RAMP2's allosteric mechanism at GCGR: cryo-EM, HDX-MS, and smFRET showed RAMP2 disorders the GCGR ECD and rearranges intracellular activation hallmarks, acting as a negative allosteric modulator that broadly inhibits downstream signaling.

    Evidence Cryo-EM at 2.9 Å of GCGR-Gs-RAMP2 complex; HDX-MS; smFRET; signaling assays

    PMID:37001505

    Open questions at the time
    • No ordered RAMP2-GCGR interface resolved — mechanism of ECD disordering is inferred rather than structurally mapped
    • Whether similar allosteric disordering occurs at PTH1R or CRFR1 unknown
  14. 2023 Medium

    Linked endothelial RAMP2 to Epac1 expression as a downstream effector maintaining vascular barrier integrity in ARDS, distinguishing RAMP2's vascular regulation role from RAMP3's anti-inflammatory role.

    Evidence DI-E-RAMP2−/− and RAMP3−/− mice in intratracheal LPS ARDS model; transcriptomic and Epac1 expression analysis

    PMID:38012983

    Open questions at the time
    • Direct transcriptional regulation of Epac1 by AM-RAMP2-cAMP pathway not demonstrated
    • Single disease model; generalizability to other forms of acute lung injury not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structural basis of AM recognition by the RAMP2-CLR complex, the full spectrum of Family B GPCRs modulated by RAMP2 in vivo, the signaling intermediates connecting AM-RAMP2 to mitochondrial homeostasis in cardiomyocytes, and whether RAMP2 allosteric mechanisms (ECD disordering) are generalizable across its non-CLR GPCR partners.
  • No high-resolution structure of the full AM–RAMP2–CLR signaling complex
  • Tissue-specific RAMP2 interactome beyond CLR, GCGR, PTH1R, CRFR1 not systematically mapped
  • Downstream pathway from AM-RAMP2 to mitochondrial function in cardiomyocytes undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2 R-HSA-9609507 Protein localization 2
Partners
CALCRLCRHR1GCGRPTH1RRAPGEF3
Complex memberships
AM1 receptor (CLR-RAMP2)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 RAMP2 forms a functional adrenomedullin (AM) receptor complex with the calcitonin receptor-like receptor (CRLR/CLR), mediating AM-induced cAMP elevation in human endothelial and vascular smooth muscle cells; RAMP2 but not RAMP1 or RAMP3 mRNA is expressed in these cells. Co-expression of RAMP2 and CRLR in HeLa EBNA and 293 EBNA cells; cAMP assay; RT-PCR FEBS letters High 10217420
2001 Seven amino acids in the extracellular N-terminal domain of RAMP2 (residues 86–92) are critical for high-affinity AM binding and AM-evoked cAMP production at the CRLR/RAMP2 receptor; deletion or alanine substitution of individual residues within this segment attenuates receptor function without disrupting cell-surface expression of the heterodimer. RAMP chimera and deletion mutant co-expression with CRLR in HEK293 cells; 125I-AM radioligand binding; cAMP assay; FACS for surface expression The Journal of biological chemistry High 11591721
2001 AM signaling in rat cardiomyocytes requires both CRLR and RAMP2 to constitute functional AM receptors; overexpression of CRLR and RAMP2 together additively potentiated AM-induced CRE-luciferase activity ~4-fold, and this response was abolished by the antagonist CGRP(8–37) or CRLR antisense. Transient transfection of cardiomyocytes with CRE-luciferase reporter; RT-PCR for RAMP2/CRLR expression; antagonist inhibition Peptides Medium 11754972
2003 CL/RAMP2 and CL/RAMP3 produce pharmacologically distinct AM receptors: AM22-52 is selective for CL/RAMP2 over CL/RAMP3, while CGRP8-37 shows the opposite selectivity in mixed-species combinations; BIBN4096BS does not antagonize AM at either receptor. Transient expression in Cos-7 cells and endogenous expression in Rat2 and L6 cells; cAMP antagonism assays with pA2 calculations British journal of pharmacology High 12970090
2008 RAMP2 is essential for vascular integrity and angiogenesis in vivo: RAMP2−/− embryos die at midgestation with vascular fragility, severe edema, hemorrhage, deformed endothelial cells detached from basement membrane, and disrupted arterial multilayer structure; expression of tight junction, adherence junction, and basement membrane molecules by ECs was diminished; in adults, reduced RAMP2 causes vascular hyperpermeability and impaired neovascularization, while EC overexpression of RAMP2 enhances capillary formation and tight junctions. RAMP2 knockout and heterozygous mouse models; EC-specific overexpression; histology; immunofluorescence; permeability assays The Journal of clinical investigation High 18097473
2013 The endothelial AM-RAMP2 system regulates vascular integrity by controlling the Rac1-GTP/RhoA-GTP ratio and cortical actin formation; loss of endothelial RAMP2 causes actin disarrangement and EC detachment, leading to vascular leakage, organ fibrosis, oxidative stress, and accelerated vascular senescence. Endothelial cell-specific RAMP2 KO mice (E-RAMP2−/−) and drug-inducible KO (DI-E-RAMP2−/−); Rac1/RhoA activity assays; in vitro actin imaging; permeability assays; histopathology Circulation High 23355623
2013 The AM-RAMP2 system is crucially involved in retinal angiogenesis: heterozygous RAMP2 KO mice show reduced pathological neovascularization with decreased VEGF and eNOS expression in OIR; inducible endothelial RAMP2 deletion causes abnormal retinal vascular patterning; AM promotes retinal EC proliferation and migration via RAMP2. RAMP2+/− and DI-E-RAMP2−/− mouse OIR model; in vitro EC proliferation/migration assays; intravitreal anti-ADM antibody treatment; RT-PCR The American journal of pathology High 23562442
2014 RAMP2 and RAMP3 have distinct functional roles in vascular biology: RAMP2 KO is embryonically lethal (essential for blood vessel development), while RAMP3 KO mice are viable but show defective lymphatic drainage and lymphatic endothelial cell migration; the AM-RAMP3 system specifically regulates lymphatic vessel function. RAMP2−/− and RAMP3−/− mouse generation; ICG lymphangiography; tail lymphedema model; scratch-wound migration assay of isolated lymphatic ECs Journal of molecular and cellular cardiology High 25264174
2014 The AM-RAMP2 system suppresses ER stress-induced tubule cell death: in renal proximal tubule cells, AM via RAMP2 suppresses PERK activation and downstream CHOP-induced apoptosis; in RAMP2+/− kidneys, tunicamycin-induced ER stress causes greater tubular damage and exogenous AM fails to rescue injury. RAMP2+/− mice; streptozotocin and tunicamycin injury models; PERK/CHOP western blotting in human RPTECs; AM rescue experiment PloS one Medium 24505304
2015 RAMP2 modulates glucagon receptor (GCGR) pharmacology by altering ligand selectivity and G protein preference; RAMP2 interaction abolishes cross-reactivity of GLP-1 receptor agonists at GCGR. Yeast reporter assays; mammalian cell functional assays; co-expression of RAMP2 with GCGR; multiple ligand competition assays The Journal of biological chemistry Medium 26198634
2016 Endothelial RAMP2 deletion promotes vascular permeability, endothelial-mesenchymal transition (EndMT)-like changes, and formation of pre-metastatic niches; RAMP2 loss leads to inflammatory cell infiltration and expression of chemotactic factors S100A8/9 and SAA3 in lung vessels, enhancing tumor metastasis; conversely, RAMP2 overexpression suppresses tumor cell adhesion to endothelial cells. DI-E-RAMP2−/− inducible KO mice; sarcoma and melanoma transplant/metastasis models; vascular permeability assays; gene expression analysis Cardiovascular research High 27307317
2017 RAMP2 co-expression with the glucagon receptor (GCGR) reduces GCGR cell-surface expression by causing its intracellular redistribution; RAMP2 influences Gαs and Gαq pathway signaling and β-arrestin recruitment at GCGR. Confocal microscopy; cell-surface ELISA; competition binding; Gαs/Gαq functional assays; β-arrestin recruitment assays; siRNA knockdown of RAMP2 Endocrinology Medium 28586439
2017 The AM-RAMP2 system in endothelial cells exerts vasoprotective effects after vascular injury: RAMP2+/− and DI-E-RAMP2−/− mice show enhanced neointima formation, increased macrophage infiltration, oxidative stress, and impaired re-endothelialization; the AM-RAMP2 system also augments proliferation and migration of endothelial progenitor cells. Wire-induced vascular injury model in RAMP2+/− and DI-E-RAMP2−/− mice; bone marrow transplant experiments; histomorphometry; EPC proliferation/migration assays Endocrinology High 28324104
2019 RAMP2 interacts with CRFR1α and CRFR1β (but not CRFR2β) to enhance their cell-surface expression; CRF stimulation causes loss of cell-surface RAMP2 when co-expressed with CRFR1 subtypes; molecular modelling identifies a smaller contact interface between RAMP2 and CRF receptors compared to CLR, and a specific residue difference (Glu vs. His) may impair CRFR2β:RAMP2 interaction. Cell-surface FLAG-RAMP2 detection across four cell lines; RT-PCR; molecular modelling Biochimica et biophysica acta. Biomembranes Medium 30826286
2019 Pathogenic RAMP2 variants cause POAG by disrupting the AM-RAMP2/CRLR-cAMP signaling pathway; mutant RAMP2 proteins aggregate in transfected cells; heterozygous Ramp2 KO in mice reduces cAMP and leads to retinal ganglion cell death. Exome sequencing; Sanger sequencing; transfection of mutant RAMP2 constructs; cAMP assays; heterozygous Ramp2 KO mouse retinal histology Genetics in medicine Medium 31000793
2021 RAMP2 alters GCGR trafficking in hepatocytes by inducing GCGR internalisation both basally and after agonist stimulation; intracellular retention of GCGR by RAMP2 biases signaling away from β-arrestin-2 recruitment toward increased Gαs activation at endosomes, producing increased short-term cAMP but enhanced lysosomal degradation long-term. Confocal microscopy; radioligand binding; WASH-complex KO MEFs; monensin trafficking inhibition; NanoBiT complementation; cAMP assays; hepatocyte-targeted AAV in lean/obese mice Molecular metabolism High 34271220
2021 Cardiomyocyte-specific RAMP2 KO mice show cardiac hypertrophy, decreased ejection fraction, increased fibrosis, reduced ventricular contractility/relaxation, and impaired mitochondrial function (fewer viable mitochondria, reduced membrane potential and respiratory capacity) after pressure overload; thus AM-RAMP2 regulates early cardiac adaptation to stress through mitochondrial homeostasis. Cardiomyocyte-specific RAMP2−/− mice; transverse aortic constriction; echocardiography; pressure-volume loops; mitochondrial membrane potential and respiratory capacity assays; isoproterenol treatment of isolated cardiomyocytes Endocrinology High 33545715
2022 RAMP2 acts as a specific allosteric modulator of the parathyroid hormone 1 receptor (PTH1R), shifting it to a preactivated state that permits faster activation in a ligand-specific manner; RAMP2 increases PTH-mediated Gi3 signaling sensitivity and increases β-arrestin2 recruitment triggered by both PTH and PTHrP. Optical FRET/BRET biosensors for PTH1R activation and downstream signaling; RAMP2 co-expression; homology modelling Proceedings of the National Academy of Sciences of the United States of America High 35914163
2023 RAMP2 acts as a negative allosteric modulator of the glucagon receptor (GCGR): RAMP2 directly interacts with GCGR, broadly inhibiting receptor-induced downstream signaling; HDX-MS shows RAMP2 enhances local flexibility in the receptor ECD and 6th transmembrane helix; smFRET demonstrates ECD disorder inhibits active and intermediate intracellular states; cryo-EM at 2.9 Å of the GCGR-Gs-RAMP2 complex shows RAMP2 does not interact with GCGR in an ordered manner but ECD is disordered with rearranged intracellular activation hallmarks. HDX-MS; smFRET; cryo-EM structure at 2.9 Å; signaling assays Cell High 37001505
2023 In the ARDS model, endothelial RAMP2 deletion reduces Epac1 expression (a regulator of vascular endothelial barrier function), impairing endothelial barrier integrity; RAMP2 primarily contributes to circulation-regulating effects of AM, while RAMP3 contributes more to inflammation regulation. DI-E-RAMP2−/− and RAMP3−/− mice; intratracheal LPS ARDS model; transcriptomic analysis; Epac1 expression assays Peptides Medium 38012983
2023 In hepatocytes, downregulation of Gata3 combined with upregulation of Ramp2 promotes proliferation of liver sinusoidal endothelial cells and hepatic revascularization after hepatectomy by shifting expression from PEDF to VEGFA. Alb-Cre-CRISPR/Cas9 AAV screening in partial hepatectomy mouse model; endothelial precursor transfusion; ALPPS model; hepatic organoids with Gata3 inhibitor; patient biopsy expression analysis Journal of hepatology Medium 37918568
2025 AM/RAMP2 signaling enhances vascular barrier integrity, anti-inflammatory phenotype, and endothelial homeostasis in human pulmonary endothelial cells under shear stress; blockade of RAMP2 completely attenuates the ADM-induced upregulation of endothelial homeostatic markers (CDH5, NOS3, TEK, S1PR1), anti-coagulation (THBD increase, F3 decrease), and aerocyte marker EDNRB. ECIS and XperT permeability assays; shear stress perfusion system (15 dynes/cm2); RAMP2 blockade; gene expression analysis Cells Medium 41597226

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity. The Journal of clinical investigation 161 18097473
2003 CL/RAMP2 and CL/RAMP3 produce pharmacologically distinct adrenomedullin receptors: a comparison of effects of adrenomedullin22-52, CGRP8-37 and BIBN4096BS. British journal of pharmacology 117 12970090
1999 The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells. FEBS letters 113 10217420
2004 Effects of adrenomedullin on endothelial cells in the multistep process of angiogenesis: involvement of CRLR/RAMP2 and CRLR/RAMP3 receptors. International journal of cancer 110 14712479
2013 Vascular endothelial adrenomedullin-RAMP2 system is essential for vascular integrity and organ homeostasis. Circulation 81 23355623
2007 Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation. Clinical cancer research : an official journal of the American Association for Cancer Research 74 17671114
2015 Modulation of Glucagon Receptor Pharmacology by Receptor Activity-modifying Protein-2 (RAMP2). The Journal of biological chemistry 60 26198634
2020 Exosomal lncRNA RAMP2-AS1 Derived from Chondrosarcoma Cells Promotes Angiogenesis Through miR-2355-5p/VEGFR2 Axis. OncoTargets and therapy 57 32368088
2001 The seven amino acids of human RAMP2 (86) and RAMP3 (59) are critical for agonist binding to human adrenomedullin receptors. The Journal of biological chemistry 53 11591721
2016 The endothelial adrenomedullin-RAMP2 system regulates vascular integrity and suppresses tumour metastasis. Cardiovascular research 51 27307317
2023 Negative allosteric modulation of the glucagon receptor by RAMP2. Cell 44 37001505
2003 Changes in the expression of calcitonin receptor-like receptor, receptor activity-modifying protein (RAMP) 1, RAMP2, and RAMP3 in rat uterus during pregnancy, labor, and by steroid hormone treatments. Biology of reproduction 41 12801991
2015 Adrenomedullin-RAMP2 System in Vascular Endothelial Cells. Journal of atherosclerosis and thrombosis 35 26040754
2014 Functional differentiation of RAMP2 and RAMP3 in their regulation of the vascular system. Journal of molecular and cellular cardiology 34 25264174
2011 Research resource: Haploinsufficiency of receptor activity-modifying protein-2 (RAMP2) causes reduced fertility, hyperprolactinemia, skeletal abnormalities, and endocrine dysfunction in mice. Molecular endocrinology (Baltimore, Md.) 32 21566080
2017 RAMP2 Influences Glucagon Receptor Pharmacology via Trafficking and Signaling. Endocrinology 29 28586439
2001 Adrenomedullin signalling in cardiomyocytes is dependent upon CRLR and RAMP2 expression. Peptides 28 11754972
2010 Involvement of vascular endothelial growth factor signaling in CLR/RAMP1 and CLR/RAMP2-mediated pro-angiogenic effect of intermedin on human vascular endothelial cells. International journal of molecular medicine 23 20596610
2021 Receptor Activity-Modifying Protein 2 (RAMP2) alters glucagon receptor trafficking in hepatocytes with functional effects on receptor signalling. Molecular metabolism 22 34271220
2003 Changes of adrenomedullin and receptor activity modifying protein 2 (RAMP2) in myocardium and aorta in rats with isoproterenol-induced myocardial ischemia. Peptides 22 12732346
2022 Functional modulation of PTH1R activation and signaling by RAMP2. Proceedings of the National Academy of Sciences of the United States of America 21 35914163
2014 Adrenomedullin-RAMP2 system suppresses ER stress-induced tubule cell death and is involved in kidney protection. PloS one 20 24505304
2011 Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling. Peptides 20 21782867
2022 RAMP2-AS1 inhibits CXCL11 expression to suppress malignant phenotype of breast cancer by recruiting DNMT1 and DNMT3B. Experimental cell research 19 35390315
2019 Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis. Genetics in medicine : official journal of the American College of Medical Genetics 19 31000793
2004 RAMP2 and RAMP3 mRNA levels are increased in failing rat cardiomyocytes and associated with increased responsiveness to adrenomedullin. Journal of molecular and cellular cardiology 19 15623431
2013 Adrenomedullin-RAMP2 system is crucially involved in retinal angiogenesis. The American journal of pathology 18 23562442
2017 Vasoprotective Activities of the Adrenomedullin-RAMP2 System in Endothelial Cells. Endocrinology 17 28324104
2006 Gene silencing of human RAMP2 mediated by short-interfering RNA. International journal of molecular medicine 16 16964401
2023 Balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution in postoperative liver regeneration. Journal of hepatology 15 37918568
2019 Interactions between RAMP2 and CRF receptors: The effect of receptor subtypes, splice variants and cell context. Biochimica et biophysica acta. Biomembranes 15 30826286
2014 Pathophysiological roles of adrenomedullin-RAMP2 system in acute and chronic cerebral ischemia. Peptides 14 25252154
2021 RAMP2-AS1 Regulates Endothelial Homeostasis and Aging. Frontiers in cell and developmental biology 13 33644072
2003 Changes in amount of ADM mRNA and RAMP2 mRNA in calcified vascular smooth muscle cells. Peptides 13 12668214
2017 Genetic Variants of RAMP2 and CLR are Associated with Stroke. Journal of atherosclerosis and thrombosis 12 28904253
2024 Identification of a hypoxia-suppressed lncRNA RAMP2-AS1 in breast cancer. Non-coding RNA research 9 38590436
2021 Adrenomedullin-RAMP2 and -RAMP3 Systems Regulate Cardiac Homeostasis during Cardiovascular Stress. Endocrinology 9 33545715
2001 Phenotypic changes of adrenomedullin receptor components, RAMP2, and CRLR mRNA expression in cultured rat vascular smooth muscle cells. Biochemical and biophysical research communications 9 11676473
2023 Receptor activity-modifying proteins of adrenomedullin (RAMP2/3): Roles in the pathogenesis of ARDS. Peptides 5 38012983
2025 Adrenomedullin-RAMP2 System Modulates Inflammation and Tissue Repair in Experimental Autoimmune Uveitis Via T-Cell and M2 Macrophage Regulation. Investigative ophthalmology & visual science 3 40465267
2023 RAMP2-AS1 stabilized RAPM2 mRNA through TIA1 to inhibit the progression of non-small cell lung cancer. Cellular and molecular biology (Noisy-le-Grand, France) 2 38279501
2024 Serum lncRNA RAMP2-AS1 Served as a Biomarker of Deep Vein Thrombosis Occurrence and Development in Elderly. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 1 39469176
2026 Adrenomedullin-RAMP2 Enhances Lung Endothelial Cell Homeostasis Under Shear Stress. Cells 0 41597226
2015 [Adrenomedullin-Receptor Activity-modifying Protein 2 (RAMP2) System in Retinal Angiogenesis]. Nippon Ganka Gakkai zasshi 0 26685480