Galanin receptor pathway (Homo sapiens)

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KRT1935SLC2A44, 9, 23CRP940Galanin receptor pathwayDNARAP1Bmediated NucleusIP accumulation12, 24Endoplasmic reticulumGALR2GNAQ21GNAI121GNA1221MAPK11MAPK31Y204T202MAPK1422Y182T180ZFP3622Y182Induces angiogenesis TERF2IPGTPMAPK113MAPK313AKT113CREB114S133TBC1D44, 9T642Induces adipogenesis and adipocyte differentiationRPS6KA135Proliferation of cholangiocytesCASP338CASP816CASP1216 Induces apoptosis,Inbihits cell growthMAPK132MAPK332CCND132, 38Inhibits proliferationRegulates glucosehomeostasis RHOAKCNMA136AKT16S473FOS5, 8INS4, 10, 23, 39UCP114YAP135CDKN1C38PRKCD14PPARG14Go alpha 2POMC8SLC2A44IL622ADIPOQ9PPARGC1A14BCL2L111Increase in plasmacorticosteronelevels7, 27VEGFA22VAMP223Increase in cAMP production27CDKN1A33Increase in bloodglucose level10, 28, 39PPARG23Secretion of chlorine18Ameliorate insulin resistanceCa2+ efflux36PLCGALR22, 37GALR22, 37PMCYNRAS14RAF114S259MAPK114, 34MAPK314, 34TFAP2A14 Induces cell proliferationInduces cell survivalY204Y187T202T185S473PMCYAKT16T308Y204MAPK115MAPK315Y187T202T185Modulates morphological changes in cholinergicneuronsPI3K/AKT pathway Induces apoptosisY204Y187T202T185GNAI121MAPK132MAPK332CCND132, 38Inhibits cell proliferationCDKN1B38CDKN1C38Y204Y187T202T185Role in neuro-transmitter release and cellular excitability Cl-Cl-Cl- Induces apoptosis,Inbihits cell growthStress and pain modulationPKA dependent NucleusGNAI121Adenylyl cyclaseCREB114PRKCGmediatedPI3KmediatedAdenylyl cyclasemediatedIncrease in plasmacorticosteronelevels27PKA dependentAdenylyl cyclasemediatedParacrine regulation of glucocorticoiudsecretagogueIncrease in cAMP production27Increase in plasmacorticosteronelevels27PKA dependentAdenylyl cyclasemediatedParacrine regulation of glucocorticoiudsecretagogueGALR2GALR1CREB130DNA Nucleus CREB135Anti-depressive activityY204Y187T202T185AKT117S473MAPK313Role in nociceptionand neurondevelopment Induces adipogenesisReceptorProtein up-regulationProtein ActivationmRNA up-regulationPhosphorylation site and residueLigandInduced activation and increases protein expressionInhibitionTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation Protein-protein interactionDephosphorylationLEGENDPhosphorylationNucleusCytoplasmPlasma membraneCYPMNUPDNAProteinProtein down-regulationmRNA up-regulationDNA bindingPKCdependentTBC1D429S473TBC1D44, 9T642AKT16S473SLC2A44, 9, 23MAPK1422Y182T180PPARG14GALR3GALR1CDKN1B38GALR1PMNU


Description

Galanin, a 29-30 amino acid neuropeptide named to be so, as a glycine residue occupies the position at N-terminal and an alanine residue at C-terminal. Galanin is expressed in the central and peripheral nervous systems in mammals. The galanin family of peptides includes GMAP (galanin message associated peptide), GALP (galanin-like peptide), and its splice variant alarin along with galanin. There are three known G-protein coupled receptor subtypes of galanin: GALR1, GALR2, and GALR3. Galaninergic signaling is predominantly inhibitory which mainly involves MAPK, AKT, and AC pathways. Galanin peptides have a wide range of non-neuronal functions as well as classic neuromodulatory roles, so they are often considered regulatory peptides. Galanin in general is associated with several biological functions such as arousal and sleep regulation, nociception, learning, inflammation, feeding, and neuroendocrine regulation. It is also implicated in diseases like Alzheimer's, depression, epilepsy, mood disorders, stress, anxiety, diabetes mellitus, and chronic pain. The creation of this pathway is described in Gopalakrishnan et al.

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Bibliography

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  1. Uehara T, Kanazawa T, Mizukami H, Uchibori R, Tsukahara T, Urabe M, Kume A, Misawa K, Carey TE, Suzuki M, Ichimura K, Ozawa K; ''Novel anti-tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells.''; Cancer Sci, 2014 PubMed Europe PMC Scholia
  2. Xia S, Kjaer S, Zheng K, Hu PS, Bai L, Jia JY, Rigler R, Pramanik A, Xu T, Hökfelt T, Xu ZQ; ''Visualization of a functionally enhanced GFP-tagged galanin R2 receptor in PC12 cells: constitutive and ligand-induced internalization.''; Proc Natl Acad Sci U S A, 2004 PubMed Europe PMC Scholia
  3. Elliott-Hunt CR, Pope RJ, Vanderplank P, Wynick D; ''Activation of the galanin receptor 2 (GalR2) protects the hippocampus from neuronal damage.''; J Neurochem, 2007 PubMed Europe PMC Scholia
  4. Fang P, Yu M, He B, Guo L, Huang X, Kong G, Shi M, Zhu Y, Bo P, Zhang Z; ''Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle insulin resistance through the Akt/AS160/GLUT4 pathway.''; Mech Ageing Dev, 2017 PubMed Europe PMC Scholia
  5. Amorim D, David-Pereira A, Marques P, Puga S, Rebelo P, Costa P, Pertovaara A, Almeida A, Pinto-Ribeiro F; ''A role of supraspinal galanin in behavioural hyperalgesia in the rat.''; PLoS One, 2014 PubMed Europe PMC Scholia
  6. Kanazawa T, Iwashita T, Kommareddi P, Nair T, Misawa K, Misawa Y, Ueda Y, Tono T, Carey TE; ''Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors.''; Oncogene, 2007 PubMed Europe PMC Scholia
  7. Li L; ''[San-jie cream in the treatment and prevention of muscular lumps through intramuscular injections].''; Zhonghua Hu Li Za Zhi, 1991 PubMed Europe PMC Scholia
  8. Mitsukawa K, Lu X, Bartfai T; ''Bidirectional regulation of stress responses by galanin in mice: involvement of galanin receptor subtype 1.''; Neuroscience, 2009 PubMed Europe PMC Scholia
  9. Zhang Z, Fang P, He B, Guo L, Runesson J, Langel Ü, Shi M, Zhu Y, Bo P; ''Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats.''; J Diabetes Res, 2016 PubMed Europe PMC Scholia
  10. Flynn SP, White HS; ''Regulation of glucose and insulin release following acute and repeated treatment with the synthetic galanin analog NAX-5055.''; Neuropeptides, 2015 PubMed Europe PMC Scholia
  11. Cordero-Llana O, Rinaldi F, Brennan PA, Wynick D, Caldwell MA; ''Galanin promotes neuronal differentiation from neural progenitor cells in vitro and contributes to the generation of new olfactory neurons in the adult mouse brain.''; Exp Neurol, 2014 PubMed Europe PMC Scholia
  12. Ifuku M, Okuno Y, Yamakawa Y, Izumi K, Seifert S, Kettenmann H, Noda M; ''Functional importance of inositol-1,4,5-triphosphate-induced intracellular Ca2+ mobilization in galanin-induced microglial migration.''; J Neurochem, 2011 PubMed Europe PMC Scholia
  13. Banerjee R, Henson BS, Russo N, Tsodikov A, D'Silva NJ; ''Rap1 mediates galanin receptor 2-induced proliferation and survival in squamous cell carcinoma.''; Cell Signal, 2011 PubMed Europe PMC Scholia
  14. Kim A, Park T; ''Diet-induced obesity regulates the galanin-mediated signaling cascade in the adipose tissue of mice.''; Mol Nutr Food Res, 2010 PubMed Europe PMC Scholia
  15. Keimpema E, Zheng K, Barde SS, Berghuis P, Dobszay MB, Schnell R, Mulder J, Luiten PG, Xu ZD, Runesson J, Langel Ü, Lu B, Hökfelt T, Harkany T; ''GABAergic terminals are a source of galanin to modulate cholinergic neuron development in the neonatal forebrain.''; Cereb Cortex, 2014 PubMed Europe PMC Scholia
  16. Li Y, Mei Z, Liu S, Wang T, Li H, Li XX, Han S, Yang Y, Li J, Xu ZD; ''Galanin Protects from Caspase-8/12-initiated Neuronal Apoptosis in the Ischemic Mouse Brain via GalR1.''; Aging Dis, 2017 PubMed Europe PMC Scholia
  17. Hobson SA, Holmes FE, Kerr NC, Pope RJ, Wynick D; ''Mice deficient for galanin receptor 2 have decreased neurite outgrowth from adult sensory neurons and impaired pain-like behaviour.''; J Neurochem, 2006 PubMed Europe PMC Scholia
  18. Benya RV, Matkowskyj KA, Danilkovich A, Hecht G; ''Galanin causes Cl- secretion in the human colon. Potential significance of inflammation-associated NF-kappa B activation on galanin-1 receptor expression and function.''; Ann N Y Acad Sci, 1998 PubMed Europe PMC Scholia
  19. Rajarao SJ, Platt B, Sukoff SJ, Lin Q, Bender CN, Nieuwenhuijsen BW, Ring RH, Schechter LE, Rosenzweig-Lipson S, Beyer CE; ''Anxiolytic-like activity of the non-selective galanin receptor agonist, galnon.''; Neuropeptides, 2007 PubMed Europe PMC Scholia
  20. Badie-Mahdavi H, Lu X, Behrens MM, Bartfai T; ''Role of galanin receptor 1 and galanin receptor 2 activation in synaptic plasticity associated with 3',5'-cyclic AMP response element-binding protein phosphorylation in the dentate gyrus: studies with a galanin receptor 2 agonist and galanin receptor 1 knockout mice.''; Neuroscience, 2005 PubMed Europe PMC Scholia
  21. Wittau N, Grosse R, Kalkbrenner F, Gohla A, Schultz G, Gudermann T; ''The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to G(q), G(i) and G(12) proteins.''; Oncogene, 2000 PubMed Europe PMC Scholia
  22. Banerjee R, Van Tubergen EA, Scanlon CS, Vander Broek R, Lints JP, Liu M, Russo N, Inglehart RC, Wang Y, Polverini PJ, Kirkwood KL, D'Silva NJ; ''The G protein-coupled receptor GALR2 promotes angiogenesis in head and neck cancer.''; Mol Cancer Ther, 2014 PubMed Europe PMC Scholia
  23. Bu L, Chang X, Cheng X, Yao Q, Su B, Sheng C, Qu S; ''Activated central galanin type 1 receptor alleviated insulin resistance in diabetic rat muscle.''; J Neurosci Res, 2016 PubMed Europe PMC Scholia
  24. Webling K, Runesson J, Lang A, Saar I, Kofler B, Langel Ü; ''Ala5-galanin (2-11) is a GAL2R specific galanin analogue.''; Neuropeptides, 2016 PubMed Europe PMC Scholia
  25. Osmond RI, Martin-Harris MH, Crouch MF, Park J, Morreale E, Dupriez VJ; ''G-protein-coupled receptor-mediated MAPK and PI3-kinase signaling is maintained in Chinese hamster ovary cells after γ-irradiation.''; J Biomol Screen, 2012 PubMed Europe PMC Scholia
  26. Constantin S, Wray S; ''Galanin Activates G Protein Gated Inwardly Rectifying Potassium Channels and Suppresses Kisspeptin-10 Activation of GnRH Neurons.''; Endocrinology, 2016 PubMed Europe PMC Scholia
  27. Andreis PG, Malendowicz LK, Rebuffat P, Spinazzi R, Ziolkowska A, Nussdorfer GG; ''Galanin enhances corticosterone secretion from dispersed rat adrenocortical cells through the activation of GAL-R1 and GAL-R2 receptors coupled to the adenylate cyclase-dependent signaling cascade.''; Int J Mol Med, 2007 PubMed Europe PMC Scholia
  28. Tang G, Wang Y, Park S, Bajpayee NS, Vi D, Nagaoka Y, Birnbaumer L, Jiang M; ''Go2 G protein mediates galanin inhibitory effects on insulin release from pancreatic β cells.''; Proc Natl Acad Sci U S A, 2012 PubMed Europe PMC Scholia
  29. Fang P, Zhang L, Yu M, Sheng Z, Shi M, Zhu Y, Zhang Z, Bo P; ''Activiated galanin receptor 2 attenuates insulin resistance in skeletal muscle of obese mice.''; Peptides, 2018 PubMed Europe PMC Scholia
  30. Borroto-Escuela DO, Narvaez M, Di Palma M, Calvo F, Rodriguez D, Millon C, Carlsson J, Agnati LF, Garriga P, Díaz-Cabiale Z, Fuxe K; ''Preferential activation by galanin 1-15 fragment of the GalR1 protomer of a GalR1-GalR2 heteroreceptor complex.''; Biochem Biophys Res Commun, 2014 PubMed Europe PMC Scholia
  31. Hawes JJ, Brunzell DH, Wynick D, Zachariou V, Picciotto MR; ''GalR1, but not GalR2 or GalR3, levels are regulated by galanin signaling in the locus coeruleus through a cyclic AMP-dependent mechanism.''; J Neurochem, 2005 PubMed Europe PMC Scholia
  32. Kanazawa T, Misawa K, Misawa Y, Maruta M, Uehara T, Kawada K, Nagatomo T, Ichimura K; ''Galanin receptor 2 utilizes distinct signaling pathways to suppress cell proliferation and induce apoptosis in HNSCC.''; Mol Med Rep, 2014 PubMed Europe PMC Scholia
  33. Tofighi R, Joseph B, Xia S, Xu ZQ, Hamberger B, Hökfelt T, Ceccatelli S; ''Galanin decreases proliferation of PC12 cells and induces apoptosis via its subtype 2 receptor (GalR2).''; Proc Natl Acad Sci U S A, 2008 PubMed Europe PMC Scholia
  34. Hawes JJ, Narasimhaiah R, Picciotto MR; ''Galanin and galanin-like peptide modulate neurite outgrowth via protein kinase C-mediated activation of extracellular signal-related kinase.''; Eur J Neurosci, 2006 PubMed Europe PMC Scholia
  35. McMillin M, Frampton G, Grant S, DeMorrow S; ''The Neuropeptide Galanin Is Up-Regulated during Cholestasis and Contributes to Cholangiocyte Proliferation.''; Am J Pathol, 2017 PubMed Europe PMC Scholia
  36. Pan NC, Bai YF, Yang Y, Hökfelt T, Xu ZQ; ''Activation of galanin receptor 2 stimulates large conductance Ca(2+)-dependent K(+) (BK) channels through the IP3 pathway in human embryonic kidney (HEK293) cells.''; Biochem Biophys Res Commun, 2014 PubMed Europe PMC Scholia
  37. Xia S, Kjaer S, Zheng K, Hu PS, Xu T, Hökfelt T, Xu ZQ; ''Constitutive and ligand-induced internalization of EGFP-tagged galanin R2 and Rl receptors in PC12 cells.''; Neuropeptides, 2005 PubMed Europe PMC Scholia
  38. Kanazawa T, Kommareddi PK, Iwashita T, Kumar B, Misawa K, Misawa Y, Jang I, Nair TS, Iino Y, Carey TE; ''Galanin receptor subtype 2 suppresses cell proliferation and induces apoptosis in p53 mutant head and neck cancer cells.''; Clin Cancer Res, 2009 PubMed Europe PMC Scholia
  39. Fang P, Shi M, Zhu Y, Zhang Z, Bo P; ''Central injection of GalR1 agonist M617 facilitates GLUT4 expression in cardiac muscle of type 2 diabetic rats.''; Exp Gerontol, 2015 PubMed Europe PMC Scholia
  40. Gopalakrishnan L, Chatterjee O, Raj C, Pullimamidi D, Advani J, Mahadevan A, Keshava Prasad TS; ''An assembly of galanin-galanin receptor signaling network.''; J Cell Commun Signal, 2020 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134603view01:30, 23 July 2024EweitzModified description
134358view05:51, 21 July 2024EgonwRemoved template comments
113773view08:08, 20 November 2020Mkutmonfix xrefs
113772view08:06, 20 November 2020Mkutmon
113770view18:03, 19 November 2020KhanspersModified description
113769view18:01, 19 November 2020KhanspersOntology Term : 'signaling pathway' added !
113768view18:01, 19 November 2020KhanspersOntology Term : 'nervous system disease' added !
113767view17:58, 19 November 2020KhanspersAdded lit ref
111988view07:12, 14 September 2020KeshavNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADIPOQProtein9370 (Entrez Gene) [Pubmed:27127795] have shown that M617 stimulates GALR1 and induces upregulation of ADIPOQ in Male Wistar Rat adipocytes.
BCL2L11Protein10018 (Entrez Gene) [Pubmed:24168112] have shown that GAL stimulates GALR2 and induces upregulation of BCL211 in HEp-2 cell line.
CDKN1AProtein1026 (Entrez Gene) [Pubmed:18272487] have shown that GAL stimulates GALR2 and induces downregulation of CDKN1A in PC12-GALR2 transfected cells.
CDKN1BProtein1027 (Entrez Gene) [Pubmed: 19276245] have shown that GAL stimulates GALR2 and induces upregulation of CDNK1B in serum starved UM-SCC-1-GALR2 cells with mutant p53 gene.
CDKN1CProtein1028 (Entrez Gene) [Pubmed: 19276245] have shown that GAL stimulates GALR2 and induces upregulation of CDKN1C in serum starved UM-SCC-1-GALR2 cells with mutant p53.
CREB1Protein1385 (Entrez Gene)
CRPProtein1401 (Entrez Gene) [Pubmed:27127795] have shown that M617 stimulates GalR1 and induces downregulation of plasma CRP in Male Wistar Rats adipocytes.
FOSProtein2353 (Entrez Gene)
  • [Pubmed:19272414]have shown that GAL stimulates GALR1 and induces the activation of FOS in Locus coeruleus of C57BL6/J mice brain.
  • [Pubmed:25405608] have shown that GAL stimulates GalR1 and  induces the upregulation of FOS in dorsomedial nucleus of the hypothalamus of Male Wistar-Han rat.
Go alpha 2
IL6Protein3569 (Entrez Gene) [Pubmed:24568968] have shown that GAL stimulates GALR2 and induces the upregulation of IL6 in UM-SCC-1 and UM-SCC-81B SSCHN cell lines.
INSProtein3630 (Entrez Gene)
  • [Pubmed:27041232] have shown that M617 stimulates GALR1 and induces downregulation of INS in diabetic rats.
  • [Pubmed:27410235] have shown that M617 stimulates GALR1 and induces downregulation of INS in blood of diabetic rats.
  • [Pubmed:25690510] have shown that NAX-5055 stimulates GALR1 and induces downregulation of INS in CF-1 mice.
  • [Pubmed:25449850] have shown that M617 stimulates GALR1 and induces downregulation of INS in cardiac muscle of diabetic and normal Male Wistar rats.
Increase in bloodglucose levelMetabolite
  • [Pubmed:25690510] have shown that NAX-5055 stimulates GALR1 and induces an increase in blood glucose levels in CF-1 mice
  • [Pubmed: 22308501] have shown that GAL stimualtes GALR1 and induces an increase in blood glucose levels in WT via Go2 signaling
  • [Pubmed:25449850] have shown that M617 stimulates GALR1 and induces decrease in glucose levels in diabetic and normal male Wistar rats.
Increase in cAMP productionMetabolite
Increase in plasmacorticosteronelevelsMetabolite[Pubmed: 17143559] have shown that GAL stimulates GALR1 and GALR2 and induces the upregulation of corticosterone in  rat adrenal zona fasciculatoreticularis cells in an adenylyl cyclase and PKA dependent manner.
KRT19Rna3880 (Entrez Gene) [Pubmed:28196718] have shown that M617 stimulates GALR1 and induces upregulation of KRT19 gene in Male Sprague- Dawley rats.
POMCProtein5443 (Entrez Gene) [Pubmed:19272414]have shown that GAL stimulates GALR1 and induces downregulation of POMC in C57BL6/J mice.
PPARGRna5468 (Entrez Gene) [Pubmed: 20183829] have shown that GAL stimulates GALR1 and GALR2 and induces upregulation of PPARG in epididymal and subcutaneous fat tissues of high fat diet fed mouse.
PPARGC1ARna10891 (Entrez Gene) [Pubmed: 20183829] have shown that GAL stimlates GALR3 and induces downregulation of PPARGC1A in epididymal and subcutaneous fat tissues in high fat diest fed mouse.
PRKCDRna5580 (Entrez Gene) [Pubmed: 20183829] have shown that GAL stimulates GALR2 and induces upregulation of PRKCD in epididymal and subcutaneous fat tissues of high fat diet fed mouse.
SLC2A4Protein6517 (Entrez Gene)
  • [Pubmed:27127795] have shown that M617 stimulates GalR1 and induces upregulation of SLC2A4 in total cell membrane and plasma membrane fractions of Male Wistar Rats adipocytes.
  • [Pubmed:27410235] have shown that M617 stimulates GALR1 and induces upregulation of SLC2A4 in plasma membrane of myocytes in diabetic rats.
  • [Pubmed: 27041232] have shown that M617 stimulates GALR1 and induces upregulation of SLC2A4 in plasma membranes of skeletal muscles in diabetic rats.
Secretion of chlorineMetabolite[Pubmed:9928160] have shown that GAL stimulates GALR1 and induces increase in Cl¯ levels in T84 cells.
TFAP2ARna7020 (Entrez Gene) [Pubmed: 20183829] have shown that GAL stimulates GALR1 and GALR2 and induces upregulation of TFAP2A in epididymal and subcutaneous fat tissues of high fat diet fed mouse.
UCP1Rna7350 (Entrez Gene) [Pubmed: 20183829] have shown that GAL stimulates GALR3 and induces downregulation of UCP1 in epididymal and subcutaneous fat tissues of high fat diet fed mouse.
VAMP2Protein6844 (Entrez Gene) [Pubmed:27410235] have shown that M617 stimulates GALR1 and induces upregulation of VAMP2 in diabetic rats.
VEGFAProtein7422 (Entrez Gene) [Pubmed:24568968] have shown that GAL stimulates GALR2 and induces the upregulation of VEGFA in UM-SCC-1 and UM-SCC-81B SSCHN cell lines.
YAP1Protein10413 (Entrez Gene) [Pubmed:28196718] have shown that GAL or M617 stimulates GALR1 and induces upregulation of YAP1 in Male Sprague-Dawley rats

Annotated Interactions

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