Galanin receptor pathway (Homo sapiens)
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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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- 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
- 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
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- 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
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- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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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External references
DataNodes
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Name | Type | Database reference | Comment |
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ADIPOQ | Protein | 9370 (Entrez Gene) | [Pubmed:27127795] have shown that M617 stimulates GALR1 and induces upregulation of ADIPOQ in Male Wistar Rat adipocytes. |
BCL2L11 | Protein | 10018 (Entrez Gene) | [Pubmed:24168112] have shown that GAL stimulates GALR2 and induces upregulation of BCL211 in HEp-2 cell line. |
CDKN1A | Protein | 1026 (Entrez Gene) | [Pubmed:18272487] have shown that GAL stimulates GALR2 and induces downregulation of CDKN1A in PC12-GALR2 transfected cells. |
CDKN1B | Protein | 1027 (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. |
CDKN1C | Protein | 1028 (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. |
CREB1 | Protein | 1385 (Entrez Gene) | |
CRP | Protein | 1401 (Entrez Gene) | [Pubmed:27127795] have shown that M617 stimulates GalR1 and induces downregulation of plasma CRP in Male Wistar Rats adipocytes. |
FOS | Protein | 2353 (Entrez Gene) |
|
Go alpha 2 | |||
IL6 | Protein | 3569 (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. |
INS | Protein | 3630 (Entrez Gene) |
|
Increase in bloodglucose level | Metabolite |
| |
Increase in cAMP production | Metabolite | ||
Increase in plasmacorticosteronelevels | Metabolite | [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. | |
KRT19 | Rna | 3880 (Entrez Gene) | [Pubmed:28196718] have shown that M617 stimulates GALR1 and induces upregulation of KRT19 gene in Male Sprague- Dawley rats. |
POMC | Protein | 5443 (Entrez Gene) | [Pubmed:19272414]have shown that GAL stimulates GALR1 and induces downregulation of POMC in C57BL6/J mice. |
PPARG | Rna | 5468 (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. |
PPARGC1A | Rna | 10891 (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. |
PRKCD | Rna | 5580 (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. |
SLC2A4 | Protein | 6517 (Entrez Gene) |
|
Secretion of chlorine | Metabolite | [Pubmed:9928160] have shown that GAL stimulates GALR1 and induces increase in Cl¯ levels in T84 cells. | |
TFAP2A | Rna | 7020 (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. |
UCP1 | Rna | 7350 (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. |
VAMP2 | Protein | 6844 (Entrez Gene) | [Pubmed:27410235] have shown that M617 stimulates GALR1 and induces upregulation of VAMP2 in diabetic rats. |
VEGFA | Protein | 7422 (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. |
YAP1 | Protein | 10413 (Entrez Gene) | [Pubmed:28196718] have shown that GAL or M617 stimulates GALR1 and induces upregulation of YAP1 in Male Sprague-Dawley rats |
Annotated Interactions
No annotated interactions