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

TitleRegulation of protein phosphatase 1I by Cdc25C-associated kinase 1 (C-TAK1) and PFTAIRE protein kinase.
Publication TypeJournal Article
Year of Publication2014
AuthorsPlatholi J, Federman A, Detert JA, Heerdt P, Hemmings HC
JournalJ Biol Chem
Date Published2014 Aug 22
KeywordsAmino Acid Sequence, Animals, Cell Line, Cyclin-Dependent Kinases, Enzyme Activation, Humans, Molecular Sequence Data, Phosphorylation, Protein Phosphatase 1, Protein-Serine-Threonine Kinases, Swine

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.

Alternate JournalJ. Biol. Chem.
PubMed ID25028520
PubMed Central IDPMC4156073
Grant ListNS 56315 / NS / NINDS NIH HHS / United States
R01 NS056315 / NS / NINDS NIH HHS / United States