Serotonin receptor 2 and STAT3 signaling (WP2079)

Mus musculus

This pathway depicts the downstream signaling of serotonin via receptor 2A, resulting in the activation of STAT3.


Egon Willighagen , Friederike Ehrhart , Eric Weitz , and Alex Pico


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Mus musculus



Cell Type Ontology


Pathway Ontology

serotonin signaling pathway


Label Type Compact URI Comment
serotonin Metabolite cas:50-67-9
Htr2a GeneProduct ensembl:ENSMUSG00000034997 5-hydroxytryptamine (serotonin) receptor 2A
Jak2 GeneProduct ensembl:ENSMUSG00000024789 Janus kinase 2
Gnaq GeneProduct ncbigene:14682 guanine nucleotide binding protein, alpha q polypeptide
Stat3 GeneProduct ncbigene:20848 signal transducer and activator of transcription


  1. Neomycin selectively inhibits 5-hydroxytryptamine-induced contraction in the guinea pig trachea. Cox DA, Watts SW, Cohen ML. J Pharmacol Exp Ther. 1996 May;277(2):954–9. PubMed Europe PMC Scholia
  2. Lack of efficacy of 5-HT2A receptor antagonists to reduce brain damage after 3 minutes of transient global cerebral ischaemia in gerbils. Piera MJ, Beaughard M, Michelin MT, Winslow E, Massingham R. Fundam Clin Pharmacol. 1995;9(6):562–8. PubMed Europe PMC Scholia
  3. Serotonin activates electrolyte transport via 5-HT2A receptor in rat colonic crypt cells. Imada-Shirakata Y, Kotera T, Ueda S, Okuma M. Biochem Biophys Res Commun. 1997 Jan 13;230(2):437–41. PubMed Europe PMC Scholia
  4. Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway. Guillet-Deniau I, Burnol AF, Girard J. J Biol Chem. 1997 Jun 6;272(23):14825–9. PubMed Europe PMC Scholia
  5. Mechanisms of serotonin-induced Ca2+ responses in mesangial cells. Goppelt-Struebe M, Stroebel M. Naunyn Schmiedebergs Arch Pharmacol. 1997 Aug;356(2):240–7. PubMed Europe PMC Scholia
  6. Fluoxetine gradually increases [125I]DOI-labelled 5-HT2A/2C receptors in the hypothalamus without changing the levels of Gq- and G11-proteins. Li Q, Muma NA, Battaglia G, Van de Kar LD. Brain Res. 1997 Nov 14;775(1–2):225–8. PubMed Europe PMC Scholia
  7. Sexual functioning in depressed outpatients taking mirtazapine. Boyarsky BK, Haque W, Rouleau MR, Hirschfeld RM. Depress Anxiety. 1999;9(4):175–9. PubMed Europe PMC Scholia
  8. Occurrence of a transcription factor, signal transducer and activators of transcription 3 (Stat3), in the postsynaptic density of the rat brain. Murata S, Usuda N, Okano A, Kobayashi S, Suzuki T. Brain Res Mol Brain Res. 2000 May 31;78(1–2):80–90. PubMed Europe PMC Scholia
  9. The information content of spontaneous retinal waves. Butts DA, Rokhsar DS. J Neurosci. 2001 Feb 1;21(3):961–73. PubMed Europe PMC Scholia
  10. Role of STAT3 in ischemic preconditioning. Hattori R, Maulik N, Otani H, Zhu L, Cordis G, Engelman RM, et al. J Mol Cell Cardiol. 2001 Nov;33(11):1929–36. PubMed Europe PMC Scholia
  11. Chronic fluoxetine differentially affects 5-hydroxytryptamine (2A) receptor signaling in frontal cortex, oxytocin- and corticotropin-releasing factor-containing neurons in rat paraventricular nucleus. Damjanoska KJ, Van de Kar LD, Kindel GH, Zhang Y, D’Souza DN, Garcia F, et al. J Pharmacol Exp Ther. 2003 Aug;306(2):563–71. PubMed Europe PMC Scholia
  12. The sleep inducing brain lipid cis-oleamide (cOA) does not modulate serotonergic transmission in the CA1 pyramidal neurons of the hippocampus in vitro. Dougalis A, Lees G, Ganellin CR. Neuropharmacology. 2004 Jan;46(1):63–73. PubMed Europe PMC Scholia
  13. Interleukin-6-induced JAK2/STAT3 signaling pathway in endothelial cells is suppressed by hemodynamic flow. Ni CW, Hsieh HJ, Chao YJ, Wang DL. Am J Physiol Cell Physiol. 2004 Sep;287(3):C771-80. PubMed Europe PMC Scholia
  14. Signal transducer and activator of transcription 3 activation by the delta-opioid receptor via Galpha14 involves multiple intermediates. Lo RKH, Wong YH. Mol Pharmacol. 2004 Jun;65(6):1427–39. PubMed Europe PMC Scholia
  15. Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling. Kamakura S, Oishi K, Yoshimatsu T, Nakafuku M, Masuyama N, Gotoh Y. Nat Cell Biol. 2004 Jun;6(6):547–54. PubMed Europe PMC Scholia
  16. A novel mechanism for JAK2 activation by a G protein-coupled receptor, the CCK2R: implication of this signaling pathway in pancreatic tumor models. Ferrand A, Kowalski-Chauvel A, Bertrand C, Escrieut C, Mathieu A, Portolan G, et al. J Biol Chem. 2005 Mar 18;280(11):10710–5. PubMed Europe PMC Scholia
  17. Hepatitis C virus (HCV) constitutively activates STAT-3 via oxidative stress: role of STAT-3 in HCV replication. Waris G, Turkson J, Hassanein T, Siddiqui A. J Virol. 2005 Feb;79(3):1569–80. PubMed Europe PMC Scholia
  18. A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells. Flowers LO, Subramaniam PS, Johnson HM. Oncogene. 2005 Mar 17;24(12):2114–20. PubMed Europe PMC Scholia