Yamamura, Yukio University of Tokushima
Morigaki, Ryoma University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kasahara, Jiro University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Yokoyama, Hironori University of Tokushima
Tanabe, Akie University of Tokushima
Koizumi, Hidetaka University of Tokushima
Nagahiro, Shinji University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kaji, Ryuji University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
cyclin-dependent kinase 5
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.
Frontiers in Cellular Neuroscience
Frontiers Media S.A.
© 2013 Yamamura, Morigaki, Kasahara, Yokoyama, Tanabe, Okita, Koizumi, Nagahiro, Kaji and Goto. This is an open-access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/3.0/), which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
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fncel_7_12.pdf 4.93 MB