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Ligand-induced activation of ERK1/2 signaling by constitutively active Gs-coupled 5-HT receptors

	author = {Ping Liu and Yu-ling Yin and Ting Wang and Li Hou and Xiao-xi Wang and Man Wang and Guan-guan Zhao and Yi Shi and H. Eric Xu and Yi Jiang},
	title = {Ligand-induced activation of ERK1/2 signaling by constitutively active G s -coupled 5-HT receptors},
	journal = {Acta Pharmacologica Sinica},
	volume = {40},
	number = {9},
	year = {2019},
	keywords = {},
	abstract = {5-HT4R, 5-HT6R, and 5-HT7A,/SUB.R are three constitutively active Gs-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 Gs 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 Gs signaling has also been widely studied. In this study, we investigated these two signaling pathways originating from the three Gs-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 Gs signaling. This indicates that Gs signaling alone is not sufficient for ERK1/2 activation in these three 5-HT receptors. In addition to Gs, 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 Gs, β-arrestin, and Fyn.},
	url = {}