Frontiers in Cellular Neuroscience (Feb 2013)

Dopamine signaling negatively regulates striatal phosphorylation of Cdk5 at tyrosine 15 in mice.

  • Yukio eYamamura,
  • Ryoma eMorigaki,
  • Jiro eKasahara,
  • Hironori eYokoyama,
  • Akie eTanabe,
  • Shinya eOkita,
  • Hidetaka eKoizumi,
  • Shinji eNagahiro,
  • Ryuji eKaji,
  • Satoshi eGoto

DOI
https://doi.org/10.3389/fncel.2013.00012
Journal volume & issue
Vol. 7

Abstract

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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 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.

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