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


ABSTRACT: 5-HT4R, 5-HT6R, and 5-HT7AR 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 ?-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, ?-arrestin, and Fyn.

SUBMITTER: Liu P 

PROVIDER: S-EPMC6786432 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Ligand-induced activation of ERK1/2 signaling by constitutively active G<sub>s</sub>-coupled 5-HT receptors.

Liu Ping P   Yin Yu-Ling YL   Wang Ting T   Hou Li L   Wang Xiao-Xi XX   Wang Man M   Zhao Guan-Guan GG   Shi Yi Y   Xu H Eric HE   Jiang Yi Y  

Acta pharmacologica Sinica 20190304 9


5-HT<sub>4</sub>R, 5-HT<sub>6</sub>R, and 5-HT<sub>7A</sub>R are three constitutively active G<sub>s</sub>-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<sub>s</sub> 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  ...[more]

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