The reference OMIM entry for this protein is 176875

Protein phosphatase 1, catalytic subunit, alpha isoform; ppp1ca
Protein phosphatase 1, alpha subunit; ppp1a

DESCRIPTION

Protein phosphorylation, a crucial posttranslational modification that controls many diverse cellular functions, is dependent on the opposing actions of protein kinases and protein phosphatases. Protein phosphatase-1 (PP1) is 1 of 4 major protein phosphatases identified in the cytosol of eukaryotic cells that are responsible for the dephosphorylation of serine and threonine residues in proteins. Although all 4 protein phosphatases have overlapping substrate specificities in vitro, they can be distinguished by the use of inhibitor proteins and by their dependence on metal ions. PP1 is inhibited by nanomolar concentrations of 2 thermostable proteins, inhibitor-1 (PPP1R1A; 613246) and inhibitor-2 (PPP1R2; 601792), whereas the other 3 phosphatases (see PPP2CA; 176915) are unaffected by these inhibitors. PPP1CA encodes a catalytic subunit of PP1 that forms heterodimers with various PP1 regulatory subunits (e.g., PPP1R3A; 600917). These regulatory subunits target PP1 to particular subcellular locations and selectively enhance its activity toward certain substrates (Cohen and Cohen, 1989).

CLONING

Barker et al. (1990) isolated a cDNA encoding 1 isoform (PP1-alpha) of the catalytic subunit of human protein phosphatase-1. Using 2 regions conserved within PP1 genes, Song et al. (1993) amplified a partial PPP1CA sequence by PCR, and they screened a cDNA library using this product to obtain a full-length clone. The deduced 330-amino acid protein shows complete concordance with the rabbit protein. Northern blot analysis revealed 1.6-kb transcript.

GENE FUNCTION

Genoux et al. (2002) demonstrated that PP1 determined the efficacy of learning and memory by limiting acquisition and favoring memory decline. When PP1 is genetically inhibited during learning, short intervals between training episodes are sufficient for optimal performance. Enhanced learning correlates with increased phosphorylation of CREB (123810), of CAMKII (114078), and of the GLUR1 subunit of the AMPA receptor (138248); it also correlates with CREB-dependent gene expression that, in control mice, occurs only with widely distributed training. Inhibition to PP1 prolongs memory when induced after learning, suggesting that PP1 also promotes forgetting. Genoux et al. (2002) suggested that this property may account for age-related cognitive decay, as old mutant mice had preserved memory. They concluded that their findings emphasized the physiologic importance of PP1 as a suppressor of learning and memory, and as a potential mediator of cognitive decline during aging. Danial et al. (2003) undertook a proteomic analysis to assess whether BAD (603167) might participate in mitochondrial physiology. In liver mitochondria, BAD resides in a functional holoenzyme complex together with protein kinase A (see 176911) and PP1 catalytic units, WAVE1 (605035) as an A kinase-anchoring protein, and glucokinase (138079). Using mitochondria from hepatocytes of Bad-deficient mice, Danial et al. (2003) demonstrated that BAD is required to assemble the complex, the lack of which results in diminished mitochondria-based glucokinase activity and blunted mitochondrial respiration in response to glucose. Glucose deprivation results in dephosphorylation of BAD, and BAD-dependent cell death. In CT26 mouse colon cancer cells, Obeid et al. (2007) demonstrated that anthracyclins induced immunogenic cell death by way of a rapid, preapoptotic translocation of calreticulin (CALR; ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 176875 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).