Yun, Hyung-Mun Kim, Sunoh Kim, Hyun-Ji Kostenis, Evi Kim, Jae Il Seong, Jae Young Baik, Ja-Hyun Rhim, Hyewhon 2024-01-21T01:32:18Z 2024-01-21T01:32:18Z 2021-09-04 2007-02-23 0021-9258 https://pubs.kist.re.kr/handle/201004/134637 The human 5-HT6 receptor (5-HT6R) is one of the latest cloned receptors among the known 5-HT receptors. Its abundant distribution in the limbic region, which participates in the control of mood and emotion and is involved in nervous system diseases such as depression and Alzheimer disease, has caused it to generate much interest. However, the cellular mechanisms of 5-HT6R are poorly understood. In the present study we found, using a yeast two-hybrid assay, that the carboxyl-terminal region of 5-HT6R interacts with the Fyn-tyrosine kinase. We also determined using a glutathione S-transferase pulldown assay that this interaction was mediated through the SH3 domain of Fyn and confirmed this by co-immunoprecipitation assays in two different transfected cell lines as well as in adult rat brains. Immunocyto(histo)chemistry also showed prominent co-localization between 5-HT6R and Fyn in transfected cells and a similar distribution between 5-HT6R and Fyn in the rat brain. Based on this interaction, we further examined the modulation of 5-HT6R by Fyn and vice versa. In addition, we demonstrated that the activation of 5-HT6R activated the extracellular signal-regulated kinase 1/2 via an Fyn-dependent pathway. These findings suggest that Fyn may play an important role in 5-HT(6)Rmediated signaling pathways in the central nervous system. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC LONG-TERM FACILITATION TYROSINE KINASE MAP KINASE RAT-BRAIN SEROTONIN RECEPTOR ALZHEIMERS-DISEASE MOLECULAR-CLONING MESSENGER-RNA WATER MAZE CAMP The novel cellular mechanism of human 5-HT6 receptor through an interaction with Fyn Article 10.1074/jbc.M606215200 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.282, no.8, pp.5496 - 5505 JOURNAL OF BIOLOGICAL CHEMISTRY 282 8 5496 5505 scie scopus 000244482300044 2-s2.0-34247174396 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article LONG-TERM FACILITATION TYROSINE KINASE MAP KINASE RAT-BRAIN SEROTONIN RECEPTOR ALZHEIMERS-DISEASE MOLECULAR-CLONING MESSENGER-RNA WATER MAZE CAMP serotonin Fyn depression