Phosphorylation of Protein Phosphatase Inhibitor-1 by Cdk5

Details

• Personal Author:
  Bibb JA ; Czernik AJ ; Greengard P ; Hisanaga SI ; Horiuchi A ; Lan M ; Nairn AC ; Nishi A ; O'Callaghan JP ; Saito T ; Snyder GL ; Ule J
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Biochemistry Chemistry Occupational Health Safety
• Keywords:
  Biochemical-indicators Chemical-reactions Chemical-synthesis Protein-biochemistry Protein-chemistry Proteins
• ISSN:
  0021-9258
• Publisher:
  The American Society for Biochemistry and Molecular Biology, Inc.
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  276
• Issue:
  17
• NIOSHTIC Number:
  nn:20021674
• Citation:
  J Biol Chem 2001 Apr; 276(17):14490-14497
• Contact Point Address:
  Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021-6399
• Email:
  bibbj@rockvax.rockefeller.edu
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b225704898515a32b688e8d584a755d2042fc35343d0282e283dc974e7ae125609e0420d1ea5e4f28e7071ef212ed1f4a5746e9081aefc0b4eb69d3017a82104
• Download URL:
  https://stacks.cdc.gov/view/cdc/198802/cdc_198802_DS1.pdf
• File Type:
  [PDF - 396.98 KB ]