Regulation of protein phosphatase 1I by Cdc25C-associated kinase 1 (C-TAK1) and PFTAIRE protein kinase.
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.
['Platholi|Jimcy|J|', 'Federman|Anna|A|', 'Detert|Julia A|JA|', 'Heerdt|Paul|P|', 'Hemmings|Hugh C|HC|']
D000595:Amino Acid Sequence D000818:Animals D002460:Cell Line D018844:Cyclin-Dependent Kinases D004789:Enzyme Activation D006801:Humans D008969:Molecular Sequence Data D010766:Phosphorylation D054645:Protein Phosphatase 1 D017346:Protein Serine-Threonine Kinases D013552:Swine
Inhibitor 2 Cell Signaling Enzyme Enzyme Mechanism Ischemia Protein Phosphorylation