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Phosphorylation of protein phosphatase inhibitor-1 by Cdk5.
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
J Biol Chem 2001 Apr; 276(17):14490-14497
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.
Chemical-reactions; Chemical-synthesis; Protein-chemistry; Proteins; Protein-biochemistry; Biochemical-indicators; Biochemistry
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021-6399
Issue of Publication
Journal of Biological Chemistry
Page last reviewed: September 2, 2020
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