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J Biol Chem. 2014 Aug 22;289(34):23893-900. doi: 10.1074/jbc.M114.557744. Epub 2014 Jul 15.

Regulation of protein phosphatase 1I by Cdc25C-associated kinase 1 (C-TAK1) and PFTAIRE protein kinase.

Author information

1
From the Departments of Anesthesiology and Pharmacology, Weill Cornell Medical College, New York, New York 10065.
2
From the Departments of Anesthesiology and.
3
From the Departments of Anesthesiology and Pharmacology, Weill Cornell Medical College, New York, New York 10065 hchemmi@med.cornell.edu.

Abstract

Protein phosphatase 1I (PP-1I) is a major endogenous form of protein phosphatase 1 (PP-1) that consists of the core catalytic subunit PP-1c and the regulatory subunit inhibitor 2 (I-2). Phosphorylation of the Thr-72 residue of I-2 is required for activation of PP-1I. We studied the effects of two protein kinases identified previously in purified brain PP-1I by mass spectrometry, Cdc25C-associated kinase 1 (C-TAK1) and PFTAIRE (PFTK1) kinase, for their ability to regulate PP-1I. Purified C-TAK1 phosphorylated I-2 in reconstituted PP-1I (PP-1c. I-2) on Ser-71, which resulted in partial inhibition of its ATP-dependent phosphatase activity and inhibited subsequent phosphorylation of Thr-72 by the exogenous activating kinase GSK-3. In contrast, purified PFTK1 phosphorylated I-2 at Ser-86, a site known to potentiate Thr-72 phosphorylation and activation of PP-1I phosphatase activity by GSK-3. These findings indicate that brain PP-1I associates with and is regulated by the associated protein kinases C-TAK1 and PFTK1. Multisite phosphorylation of the I-2 regulatory subunit of PP-1I leads to activation or inactivation of PP-1I through bidirectional modulation of Thr-72 phosphorylation, the critical activating residue of I-2.

KEYWORDS:

Cell Signaling; Enzyme; Enzyme Mechanism; Inhibitor 2; Ischemia; Protein Phosphorylation

PMID:
25028520
PMCID:
PMC4156073
DOI:
10.1074/jbc.M114.557744
[Indexed for MEDLINE]
Free PMC Article

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