{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe evolution of protein phosphatase 1 (PP1) regulation in vertebrates has been marked by an increase in the number and diversity of regulatory subunits. Recent comparative genomic analyses have identified PPP1R2C as one of several poorly characterized regulators within a broader family that modulates PP1 function. These studies suggest that, arising via gene duplication and functional conversion events during vertebrate evolution, PPP1R2C likely contributes to the fine-tuning of PP1 activity by serving as an inhibitory subunit, akin to other well‐established regulators that determine PP1’s interaction surface and cellular localization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Dissection of transcript diversity among PP1 inhibitors further supports this regulatory scheme. In studies examining alternative splicing of inhibitor proteins in human tissues, distinct isoforms were identified that vary in their amino acid composition due to in-frame and frame-shift deletions. Although these findings focused on a well-characterized form of PP1 inhibitor, they underscore the broader concept that alternative splicing is a mechanism by which PP1 regulators, potentially including PPP1R2C, achieve functional diversification in a tissue-specific manner, thereby contributing to the modulation of PP1 activity in different cellular contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "Together, these insights from evolutionary genomics and transcriptional variant analyses converge on the view that PPP1R2C is a novel and functionally significant regulator of PP1. Its presence in a spectrum of vertebrate regulators, combined with the demonstrated importance of splicing in modulating inhibitor function, suggests that PPP1R2C might play a crucial role in ensuring the spatial and temporal specificity of PP1-mediated dephosphorylation events in mammalian cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hugo Ceulemans, Willy Stalmans, Mathieu Bollen "}, {"type": "b", "children": [{"type": "t", "text": "Regulator-driven functional diversification of protein phosphatase-1 in eukaryotic evolution."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioessays (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/bies.10069"}], "href": "https://doi.org/10.1002/bies.10069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11948623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11948623"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hsin-tzu Liu, Ta-hsien Lin, Hann-chorng Kuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the alternative splice products encoded by the human protein phosphatase inhibitor-1 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/bbrc.2002.6602"}], "href": "https://doi.org/10.1006/bbrc.2002.6602"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11883959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11883959"}]}]}]}