[The role of transactivation as a signal transduction mechanism in the central nervous system].
Transactivation represents the process whereby G-protein coupled receptors (GPCRs) activate receptor tyrosine kinases (RTKs), which are receptors for several neurotrophic factors and growth factors, with a subsequent downstream signaling such as mitogen-activated protein kinase (MAPK). Transactivation has been shown to be involved in the pathophysiology of cardiac hypertrophy and chronic kidney diseases, and it is targeted to develop novel therapeutic agents for these diseases. Recent accumulating evidence indicates that monoamines as well as neurotrophic factors and growth factors are thought to be involved in the therapeutic effects for psychiatric disorders. We have reported that serotonin (5-HT), which is important for the effect of antidepressant, increases glial cell line-derived neurotrophic factor (GDNF) via the 5-HT2R-mediated fibroblast growth factor receptor 2 transactivation pathway in glial cells (Tsuchioka et al, 2008). Transactivation in the CNS may play a role in the crosstalk between receptors for neurotransmitters, such as monoamines, and RTKs. Thus, transactivation will be an important basis for producing novel treatment strategies for psychiatric disorders. In this review, we outline a role of transacitvation in the CNS by explaining the concept and the mechanism of transactivation and summarizing recent reports about it in the CNS with our results.
Tsuchioka
Mami
M
Division of Psychiatry and Neuroscience, Institute for Clinical Research, Kure, 737-0023 Japan.
Hisaoka
Kazue
K
Nakata
Yoshihiro
Y
Takebayashi
Minoru
M
D000818:Animals; D002490:Central Nervous System / Q000502:physiology*; D054388:Receptors, CCR / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
D054388:Receptors, CCR; D017468:Receptors, Fibroblast Growth Factor