%0 Journal Article %T Ligand-induced activation of ERK1/2 signaling by constitutively active G s -coupled 5-HT receptors %A Liu Ping %A Yin Yu-ling %A Wang Ting %A Hou Li %A Wang Xiao-xi %A Wang Man %A Zhao Guan-guan %A Shi Yi %A Xu H. Eric %A Jiang Yi %J Acta Pharmacologica Sinica %D 2019 %B 2019 %9 %! Ligand-induced activation of ERK1/2 signaling by constitutively active G s -coupled 5-HT receptors %K %X 5-HT 4 R, 5-HT 6 R, and 5-HT 7A,/SUB.R are three constitutively active G s -coupled 5-HT receptors that have key roles in brain development, learning, memory, cognition, and other physiological processes in the central nervous system. In addition to G s signaling cascade mediated by these three 5-HT receptors, the ERK1/2 signaling which is dependent on cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activation downstream of G s signaling has also been widely studied. In this study, we investigated these two signaling pathways originating from the three G s -coupled 5-HT receptors in AD293 cells. We found that the phosphorylation and activation of ERK1/2 are ligand-induced, in contrast to the constitutively active G s signaling. This indicates that G s signaling alone is not sufficient for ERK1/2 activation in these three 5-HT receptors. In addition to G s , we found that β-arrestin and Fyn are essential for the activation of ERK1/2. Together, these results put forth a novel mechanism for ERK1/2 activation involving the cooperative action of G s , β-arrestin, and Fyn. %U http://www.chinaphar.com/article/view/10019 %V 40 %N 9 %P 1157–1167 %@ 1745-7254