Entry Name Relaxin signaling pathway - Monodelphis domestica (gray short-tailed opossum)
Description Human relaxin-2 ("relaxin"), originally identified as a peptidic hormone of pregnancy, is now known to exert a range of pleiotropic effects including vasodilatory, anti-fibrotic and angiogenic effects in both males and females. It belongs to the so-called relaxin peptide family which includes the insulin-like peptides INSL3 and INSL5, and relaxin-3 (H3) as well as relaxin. INSL3 has clearly defined specialist roles in male and female reproduction, relaxin-3 is primarily a neuropeptide involved in stress and metabolic control, and INSL5 is widely distributed particularly in the gastrointestinal tract. These members of relaxin peptide family exert such effects binding to different kinds of receptors, classified as relaxin family peptide (RXFP) receptors: RXFP1, RXFP2, RXFP3, and RXFP4. These G protein-coupled receptors predominantly bind relaxin, INSL3, relaxin-3, and INSL-5, respectively. RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. Both RXFP3 and RXFP4 inhibit cAMP production, and RXFP3 activate MAP kinases.
Class Organismal Systems; Endocrine systemBRITE hierarchy
Pathway map Ortholog table Organism Monodelphis domestica (gray short-tailed opossum) [GN:
mdo ]
Gene 100023453 RXFP1; relaxin/insulin like family peptide receptor 1 [KO:K04306 ]
100029582 guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632 ]
100010184 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7-like [KO:K04347 ]
100017208 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
100020067 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
100022547 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
100015046 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
100019317 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
100032726 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
100616957 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
100026442 RXFP2; relaxin/insulin like family peptide receptor 2 [KO:K04307 ]
103102289 RXFP3; relaxin/insulin like family peptide receptor 3 [KO:K08397 ]
100018774 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
100018285 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
554197 NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828 ]
100618058 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
100029256 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
103097487 RXFP4; relaxin/insulin like family peptide receptor 4 [KO:K08398 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Bathgate RA, Halls ML, van der Westhuizen ET, Callander GE, Kocan M, Summers RJ
Title Relaxin family peptides and their receptors.
Journal Reference Authors Cernaro V, Lacquaniti A, Lupica R, Buemi A, Trimboli D, Giorgianni G, Bolignano D, Buemi M
Title Relaxin: new pathophysiological aspects and pharmacological perspectives for an old protein.
Journal Reference Authors van der Westhuizen ET, Halls ML, Samuel CS, Bathgate RA, Unemori EN, Sutton SW, Summers RJ
Title Relaxin family peptide receptors--from orphans to therapeutic targets.
Journal Reference Authors Halls ML, van der Westhuizen ET, Bathgate RA, Summers RJ
Title Relaxin family peptide receptors--former orphans reunite with their parent ligands to activate multiple signalling pathways.
Journal Reference Authors Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ
Title International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides.
Journal Reference Authors Du XJ, Bathgate RA, Samuel CS, Dart AM, Summers RJ
Title Cardiovascular effects of relaxin: from basic science to clinical therapy.
Journal Reference Authors Nistri S, Bani D
Title Relaxin receptors and nitric oxide synthases: search for the missing link.
Journal Reference Authors Samuel CS, Hewitson TD, Unemori EN, Tang ML
Title Drugs of the future: the hormone relaxin.
Journal Reference Authors Sasser JM
Title The emerging role of relaxin as a novel therapeutic pathway in the treatment of chronic kidney disease.
Journal Reference Authors Sarwar M, Du XJ, Dschietzig TB, Summers RJ
Title The actions of relaxin on the human cardiovascular system.
Journal Reference Authors Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ
Title Receptors for relaxin family peptides.
Journal Reference Authors Chow BS, Chew EG, Zhao C, Bathgate RA, Hewitson TD, Samuel CS
Title Relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to up-regulate matrix metalloproteinases: the additional involvement of iNOS.
Journal Reference Authors Samuel CS, Du XJ, Bathgate RA, Summers RJ
Title 'Relaxin' the stiffened heart and arteries: the therapeutic potential for relaxin in the treatment of cardiovascular disease.
Journal Reference Authors Wilson SS, Ayaz SI, Levy PD
Title Relaxin: a novel agent for the treatment of acute heart failure.
Journal Reference Authors Halls ML, Bathgate RA, Summers RJ
Title Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms.
Journal Reference Authors Kocan M, Ang SY, Summers RJ
Title Orthosteric, Allosteric and Biased Signalling at the Relaxin-3 Receptor RXFP3.
Journal Reference Authors van der Westhuizen ET, Werry TD, Sexton PM, Summers RJ
Title The relaxin family peptide receptor 3 activates extracellular signal-regulated kinase 1/2 through a protein kinase C-dependent mechanism.
Journal Related mdo04270 Vascular smooth muscle contraction
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