Phosphorylation of Protein Phosphatase Inhibitor-1 by Cdk5

James A. Bibb, Akinori Nishi, James P. O'Callaghan, Jernej Ule, Martin Lan, Gretchen L. Snyder, Atsuko Horiuchi, Taro Saito, Shin Ichi Hisanaga, Andrew J. Czernik, Angus C. Nairn, Paul Greengard

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Protein phosphatase inhibitor-1 is a prototypical mediator of cross-talk between protein kinases and protein phosphatases. Activation of cAMP-dependent protein kinase results in phosphorylation of inhibitor-1 at Thr-35, converting it into a potent inhibitor of protein phosphatase-1. Here we report that inhibitor-1 is phosphorylated in vitro at Ser-67 by the proline-directed kinases, Cdk1, Cdk5, and mitogen-activated protein kinase. By using phosphorylation state-specific antibodies and selective protein kinase inhibitors, Cdk5 was found to be the only kinase that phosphorylates inhibitor-1 at Ser-67 in intact striatal brain tissue. In vitro and in vivo studies indicated that phospho-Ser-67 inhibitor-1 was dephosphorylated by protein phosphatases-2A and -2B. The state of phosphorylation of inhibitor-1 at Ser-67 was dynamically regulated in striatal tissue by glutamate-dependent regulation of N-methyl-D-aspartic acid-type channels. Phosphorylation of Ser-67 did not convert inhibitor-1 into an inhibitor of protein phosphatase-1. However, inhibitor-1 phosphorylated at Ser-67 was a less efficient substrate for cAMP-dependent protein kinase. These results demonstrate regulation of a Cdk5-dependent phosphorylation site in inhibitor-1 and suggest a role for this site in modulating the amplitude of signal transduction events that involve cAMP-dependent protein kinase activation.

Original languageEnglish (US)
Pages (from-to)14490-14497
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number17
StatePublished - Apr 27 2001

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Phosphorylation
Cyclic AMP-Dependent Protein Kinases
Corpus Striatum
Chemical activation
Phospho-Specific Antibodies
CDC2 Protein Kinase
Tissue
Protein Phosphatase 2
Signal transduction
Calcineurin
Phosphoprotein Phosphatases
N-Methylaspartate
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Proline
Protein Kinases
Glutamic Acid
Signal Transduction
Brain
Phosphotransferases

ASJC Scopus subject areas

  • Biochemistry

Cite this

Bibb, J. A., Nishi, A., O'Callaghan, J. P., Ule, J., Lan, M., Snyder, G. L., ... Greengard, P. (2001). Phosphorylation of Protein Phosphatase Inhibitor-1 by Cdk5. Journal of Biological Chemistry, 276(17), 14490-14497.

Phosphorylation of Protein Phosphatase Inhibitor-1 by Cdk5. / Bibb, James A.; Nishi, Akinori; O'Callaghan, James P.; Ule, Jernej; Lan, Martin; Snyder, Gretchen L.; Horiuchi, Atsuko; Saito, Taro; Hisanaga, Shin Ichi; Czernik, Andrew J.; Nairn, Angus C.; Greengard, Paul.

In: Journal of Biological Chemistry, Vol. 276, No. 17, 27.04.2001, p. 14490-14497.

Research output: Contribution to journalArticle

Bibb, JA, Nishi, A, O'Callaghan, JP, Ule, J, Lan, M, Snyder, GL, Horiuchi, A, Saito, T, Hisanaga, SI, Czernik, AJ, Nairn, AC & Greengard, P 2001, 'Phosphorylation of Protein Phosphatase Inhibitor-1 by Cdk5', Journal of Biological Chemistry, vol. 276, no. 17, pp. 14490-14497.
Bibb JA, Nishi A, O'Callaghan JP, Ule J, Lan M, Snyder GL et al. Phosphorylation of Protein Phosphatase Inhibitor-1 by Cdk5. Journal of Biological Chemistry. 2001 Apr 27;276(17):14490-14497.
Bibb, James A. ; Nishi, Akinori ; O'Callaghan, James P. ; Ule, Jernej ; Lan, Martin ; Snyder, Gretchen L. ; Horiuchi, Atsuko ; Saito, Taro ; Hisanaga, Shin Ichi ; Czernik, Andrew J. ; Nairn, Angus C. ; Greengard, Paul. / Phosphorylation of Protein Phosphatase Inhibitor-1 by Cdk5. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 17. pp. 14490-14497.
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