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Mechanism of regulation of casein kinase I activity by group I metabotropic glutamate receptors.

Publication ,  Journal Article
Liu, F; Virshup, DM; Nairn, AC; Greengard, P
Published in: J Biol Chem
November 22, 2002

Previously, we reported that (S)-3,5-dihydroxypenylglycine (DHPG), an agonist for group I metabotropic glutamate receptors (mGluRs), stimulates CK1 and Cdk5 kinase activities in neostriatal neurons, leading to enhanced phosphorylation, respectively, of Ser-137 and Thr-75 of DARPP-32 (dopamine and cAMP-regulated phosphoprotein, 32 kDa). We have now investigated the signaling pathway that leads from mGluRs to casein kinase 1 (CK1) activation. In mouse neostriatal slices, the effect of DHPG on phosphorylation of Ser-137 or Thr-75 of DARPP-32 was blocked by the phospholipase Cbeta inhibitor, the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM), and the calcineurin inhibitor cyclosporin A. In neuroblastoma N2a cells, the effect of DHPG on the activity of transfected HA-tagged CK1(epsilon) was blocked by BAPTA/AM and cyclosporin A. In neostriatal slices, the effect of DHPG on Cdk5 activity was also abolished by BAPTA/AM and cyclosporin A, presumably through blocking activation of CK1. Metabolic labeling studies and phosphopeptide mapping revealed that a set of C-terminal sites in HA-CK1epsilon were transiently dephosphorylated in N2a cells upon treatment with DHPG, and this was blocked by cyclosporin A. A mutant CK1epsilon with a nonphosphorylatable C-terminal domain was not activated by DHPG. Together, these studies suggest that DHPG activates CK1(epsilon) via Ca(2+)-dependent stimulation of calcineurin and subsequent dephosphorylation of inhibitory C-terminal autophosphorylation sites.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 22, 2002

Volume

277

Issue

47

Start / End Page

45393 / 45399

Location

United States

Related Subject Headings

  • Type C Phospholipases
  • Tumor Cells, Cultured
  • Threonine
  • Signal Transduction
  • Serine
  • Resorcinols
  • Receptors, Metabotropic Glutamate
  • Pyrrolidinones
  • Protein Kinases
  • Phosphorylation
 

Citation

APA
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Liu, F., Virshup, D. M., Nairn, A. C., & Greengard, P. (2002). Mechanism of regulation of casein kinase I activity by group I metabotropic glutamate receptors. J Biol Chem, 277(47), 45393–45399. https://doi.org/10.1074/jbc.M204499200
Liu, Feng, David M. Virshup, Angus C. Nairn, and Paul Greengard. “Mechanism of regulation of casein kinase I activity by group I metabotropic glutamate receptors.J Biol Chem 277, no. 47 (November 22, 2002): 45393–99. https://doi.org/10.1074/jbc.M204499200.
Liu F, Virshup DM, Nairn AC, Greengard P. Mechanism of regulation of casein kinase I activity by group I metabotropic glutamate receptors. J Biol Chem. 2002 Nov 22;277(47):45393–9.
Liu, Feng, et al. “Mechanism of regulation of casein kinase I activity by group I metabotropic glutamate receptors.J Biol Chem, vol. 277, no. 47, Nov. 2002, pp. 45393–99. Pubmed, doi:10.1074/jbc.M204499200.
Liu F, Virshup DM, Nairn AC, Greengard P. Mechanism of regulation of casein kinase I activity by group I metabotropic glutamate receptors. J Biol Chem. 2002 Nov 22;277(47):45393–45399.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 22, 2002

Volume

277

Issue

47

Start / End Page

45393 / 45399

Location

United States

Related Subject Headings

  • Type C Phospholipases
  • Tumor Cells, Cultured
  • Threonine
  • Signal Transduction
  • Serine
  • Resorcinols
  • Receptors, Metabotropic Glutamate
  • Pyrrolidinones
  • Protein Kinases
  • Phosphorylation