Journal article

Possible involvement of post-dopamine D-2 receptor signalling components in the pathophysiology of schizophrenia

Shirly Amar, Galit Shaltiel, Liad Mann, Alon Shamir, Brian Dean, Elizabeth Scarr, Yuly Bersudsky, RH Belmaker, Galila Agam

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY | OXFORD UNIV PRESS | Published : 2008

Abstract

Par-4 has been suggested to mediate dopamine neurotransmission. Dopamine D2 receptor (DRD2) activation induces a signalling complex of AKT1, PP2A and beta-arrestin2 which dephosphorylates/inactivates AKT1 thereby activating GSK-3beta, transducing dopamine-dependent behaviour. DRD2 activation also results in down-regulation of PKA activity. Among other substrates PKA phosphorylates GSK-3beta. Prolonged DRD2 activation leads to its 'desensitization' which involves GRKs and beta-arrestins. beta-arrestin1 binds to phosphorylated receptors preventing further G-protein stimulation. This study examined whether Par-4, beta-arrestin1, AKT1 and GSK-3beta are involved in the pathophysiology of schizoph..

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