title: Dopamine signaling negatively regulates striatal phosphorylation of Cdk5 at tyrosine 15 in mice.
abstract: Striatal functions depend on the activity balance between the dopamine and glutamate neurotransmissions. Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5), which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) at Thr75 in the striatum. c-Abelson tyrosine kinase (c-Abl) is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5) and thereby facilitates the Cdk5 activity. We here report that Cdk5 with Tyr15 phosphorylation (Cdk5-pTyr15) is enriched in the mouse striatum, where dopaminergic stimulation inhibited phosphorylation of Tyr15-Cdk5 by acting through the D2 class dopamine receptors. Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571), a selective c-Abl inhibitor. Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum.
authors: Parkinson's Disease and Dystonia Research Center, Tokushima University Hospital, University of Tokushima Tokushima, Japan ; Department of Neurobiology and Therapeutics, Graduate School of Pharmaceutical Sciences, Institute of Health Bioscience, University of Tokushima Tokushima, Japan.
authors: Yukio
authors: Y
authors: Yamamura
authors: Ryoma
authors: R
authors: Morigaki
authors: Jiro
authors: J
authors: Kasahara
authors: Hironori
authors: H
authors: Yokoyama
authors: Akie
authors: A
authors: Tanabe
authors: Shinya
authors: S
authors: Okita
authors: Hidetaka
authors: H
authors: Koizumi
authors: Shinji
authors: S
authors: Nagahiro
authors: Ryuji
authors: R
authors: Kaji
authors: Satoshi
authors: S
authors: Goto
keywords: cell signaling; cyclin-dependent kinase 5; phosphorylation; striatum