Disease relevance of RAMP2

• On the other hand, expression levels of RAMP2 mRNA were decreased in IMR-32 cells and were not changed in NB69 cells by hypoxia [1].
• These findings indicate that adrenomedullin expression is induced during hypoxia in IMR-32 and NB69 neuroblastoma cells, but RAMP2 expression is rather suppressed under the same conditions [1].
• It is suggested that the abundant binding sites of AM in lungs are formed by CRLR and RAMP2 in healthy subjects and that their reduction should contribute to the increase of plasma AM concentrations during sepsis [2].
• The present study demonstrates for the first time that AM and its receptor component (CRLR/RAMP2) mRNAs were concomitantly expressed in various adipose tissues, whose tissue-specific upregulation was induced during the development of obesity [3].
• We examined the regulation of their expression in a rat model of renal injury and found that RAMP1, RAMP2 and CRLR expressions were markedly upregulated upon induction of fibrosis during obstructive nephropathy [4].

High impact information on RAMP2

• RAMP2 and -3 enable the same CL receptor to behave as an adrenomedullin receptor [5].
• By contrast, deletion of the C-tail from hRAMP2 disrupted transport of hCRLR to the cell surface, resulting in significant reductions in (125)I-hAM binding and evoked cAMP accumulation [6].
• The transfection efficiency for the hRAMP2 mutant was comparable with that for wild-type hRAMP2; moreover, immunocytochemical analysis showed that the mutant hRAMP2 remained within the endoplasmic reticulum [6].
• Our data suggest that ADM may prevent or reduce RA-FLS apoptosis, via up-regulation of its functional receptor CRLR/RAMP-2 [7].
• We hypothesized that a PDZ type I domain present in the C terminus of RAMP3, but not in RAMP1 or RAMP2, leads to protein-protein interactions that determine receptor trafficking [8].

Biological context of RAMP2

• Human RAMP1 was assigned to chromosome 2q36-->q37.1, RAMP2 to 17q12-->q21.1 and RAMP3 to 7p13-->p12 [9].
• The human RAMP1 and RAMP3 genes possess two introns and human RAMP2 possesses three introns [9].
• Detectable [125I]h alphaCGRP binding required the presence of hRAMP1, and the expression of CGRP binding sites was unaffected by coexpressed hRAMP2 [10].
• However, the VPAC1R-RAMP2 heterodimer displays a significant enhancement of agonist-mediated phosphoinositide hydrolysis with no change in cAMP stimulation compared with the VPAC1R alone [11].
• Since Ishikawa cells express the putative ADM-receptor CRLR-RAMP2 the production and secretion of ADM with the consecutive upregulation of Bcl-2 could establish an autocrine/paracrine mechanism rescuing malignant cells from hypoxic cell death [12].

Anatomical context of RAMP2

• This is consistent with higher levels of endogenous RAMP2 encoding messenger RNA in UMR-106, compared with COS-7 cells [10].
• 4. L6, SK-N-MC and Col-29 cells expressed mRNA for RAMP1 and RAMP2 but Rat-2 fibroblasts had only RAMP2 [13].
• The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells [14].
• Using specific oligonucleotides we have determined the expression of RAMP1, RAMP2 and RAMP3 mRNAs in the rat central nervous system by in situ hybridization [15].
• Northern blot analyses revealed that the RAMP family genes are expressed in various tissues with different tissue specificity; RAMP1 is abundantly expressed in the brain, fat, thymus, and spleen, RAMP2 in the lung, spleen, fat, and aorta, while RAMP3 is most abundant in the kidney and lung [16].

Associations of RAMP2 with chemical compounds

• There is little sequence identity between hRAMP3 residues 59-65 and hRAMP2 residues 86-92; moreover, substituting alanine for Trp(86) (Ala(87)), Met(88), Ile(89), Ser(90), Arg(91), or Pro(92) of hRAMP2 had no effect on AM-evoked cAMP production [17].
• Treatment with cobalt chloride or desferrioxamine mesylate decreased expression levels of RAMP2 mRNA in both IMR-32 and NB69 cells [1].
• The RAMP1 mRNA expression was elevated with doses of dexamethasone ranging from 10(-10) to 10(-7) M, thus a 5-fold increase in the ratio between RAMP1 and RAMP2 was observed with the lowest dose of dexamethasone and a 2-fold rise at 10(-7) M [18].
• A single transcript of 0.8 kb for RAMP2 was also seen in the follicle and corpus luteum, the level of RAMP2 mRNA was relatively high in the preovulatory follicle and RAMP2 was present in the corpus luteum [19].
• Cysteine residues in the extracellular loops of hCRLR and in the extracellular domain of hRAMP2 thus appear to play distinct roles in the cell surface expression and function of the receptor heterodimer [20].

Physical interactions of RAMP2

• More detailed analysis showed that deletion of hRAMP2 residues 86-92 significantly attenuated high-affinity (125)I-AM binding and AM-evoked cAMP production despite full cell surface expression of the receptor heterodimer and that deletion of hRAMP3 residues 59-65 had a similar effect [17].

Regulatory relationships of RAMP2

• RAMP2 gene silencing was determined in HUVECs by measuring RAMP2 mRNA levels in transfected and control cells by real-time polymerase chain reaction [21].

Other interactions of RAMP2

• Thus, the respective C-tails of hRAMP2 and -3 differentially affect hCRLR surface delivery and internalization [6].
• In COS-7 cells, the results were comparable, but rCRLR required coexpressed hRAMP2 for ADM receptor function [10].
• We suggest that the human RAMP2 molecule does not interact with the sCL receptor because of major differences in the sequences of the salmon CL receptor and the mammalian CL receptor [22].
• The selectivity for AM and CGRP agonists and antagonists of human, rat, porcine and bovine CL receptors, co-expressed with RAMP2 and -3, has been studied in different cell types [23].
• RAMP 2 or vector cotransfection did not cause significant increases in specific amylin binding [24].

Analytical, diagnostic and therapeutic context of RAMP2

• RAMP2 and RAMP3 mRNA were not detectable by in-situ hybridization [25].
• Semi-quantitative RT-PCR analysis showed that the gene expression of calcitonin receptor-like receptor and receptor-activity-modifying protein (RAMP)1, RAMP2 and RAMP3 in ventricular myocardia were up-regulated by 79% (P<0.01), 48% (P<0.01), 31% (P<0.05) and 130% (P<0.01), respectively, compared with controls [26].

References