PPP1R2

What is PPP1R2 protein?

PPP1R2 gene (protein phosphatase 1 regulatory inhibitor subunit 2) is a protein coding gene which situated on the long arm of chromosome 3 at locus 3q29. PP1 is one of the main serine/threonine phosphatases in eukaryotic organisms, playing a critical role in the regulation of numerous cellular processes by removing phosphate groups from its target proteins. PPP1R2 binds to the catalytic subunit of PP1, thereby inhibiting its activity. PPP1R2 is involved in a variety of cellular processes, including cell division, cell motility, and cell signaling. It has been identified as a negative regulator of PP1 and an activator of Aurora A Kinase (AURKA), which are both crucial for proper cell cycle progression and cell division. Additionally, PPP1R2 has been found to play a role in the development and maturation of sperm, as it is expressed at high levels in developing spermatogonic cells and is involved in the regulation of sperm motility. The PPP1R2 protein is consisted of 205 amino acids and PPP1R2 molecular weight is approximately 23.0 kDa.

What is the function of PPP1R2 protein?

PP1 is one of the main serine/threonine phosphatases in eukaryotic cells, playing a crucial role in the regulation of a wide array of cellular processes by removing phosphate groups from its target proteins. It plays a role in the development and maturation of sperm, as it is expressed at high levels in developing spermatogonic cells and is implicated in the regulation of sperm motility. Additionally, PPP1R2 is suggested to participate in the regulation of the cell cycle and is associated with the maintenance of central spindle architecture by coordinating the activities of AURKA and PP1. Furthermore, PPP1R2 has been identified as a potential drug target and biomarker in the medical field due to its involvement in various cellular processes and its potential role in tumorigenesis.

Fig1. Schematic diagram of how PP1y2 is regulated by its inhibitors in sperm during its transition from caput to caudal epididymis. (Suranjana Goswami, 2019)

PPP1R2 Related Signaling Pathway

PPP1R2 is involved in the regulation of the cell cycle, particularly in the coordination of centrosome number and mitotic spindle function. As part of the cAMP-dependent protein kinase (PKA) signaling pathway, PPP1R2 may play a role in the activation of PKA through G-protein-coupled receptors (GPCRs) and the subsequent regulation of various cellular processes. PPP1R2 is known to be involved in the regulation of glycogen metabolism, potentially affecting the activity of glycogen synthase, an enzyme important for glycogen synthesis. PPP1R2 is suggested to be involved in the regulation of Aurora kinases, which are important for proper cell division and are often implicated in cancer.

PPP1R2 Related Diseases

PPP1R2 is associated with several diseases, predominantly linked to the function of PP1γ2 isoform present in mammalian testis and sperm, which suggests its role in male fertility. PPP1R2 is also implicated in cataract formation, specifically in the development of various types of cataract, including posterior polar cataract. Furthermore, it has been noted in the context of pulmonary talcosis, which is related to pneumoconiosis due to talc. The association of PPP1R2 with these diseases underscores its importance in cellular processes and its potential as a therapeutic target.

Bioapplications of PPP1R2

Its involvement in fundamental cellular processes such as cell cycle regulation, cell signaling, and metabolism positions it as a key player in the development of therapeutic strategies for diseases like cancer. PPP1R2's ability to regulate the activity of PP1, a phosphatase implicated in numerous cellular functions, makes it an attractive target for drug development. As a biomarker, PPP1R2 holds promise for personalized medicine approaches, where its expression levels can indicate the presence and progression of diseases, including tumors.

Case Study 1: Alan-Michael Bresch, 2020

Maintenance of centrosome number in cells is essential for accurate distribution of chromosomes at mitosis and is dependent on both proper centrosome duplication during interphase and their accurate distribution to daughter cells at cytokinesis. Two essential regulators of cell cycle progression are protein phosphatase 1 (PP1) and Aurora A kinase (AURKA), and their activities are each regulated by the PP1 regulatory subunit, protein phosphatase 1 regulatory subunit 2 (PPP1R2). An increase in centrosome number after overexpression of these proteins in cells. Each of these proteins is found on the midbody in telophase and overexpression of PPP1R2 and its mutants increased cell ploidy and disrupted cytokinesis. This suggests that the increase in centrosome number observed in PPP1R2 overexpressing cells was a consequence of errors in cell division. Furthermore, overexpression of PPP1R2 and its mutants increased midbody length and disrupted midbody architecture. Additionally, researchers show that overexpression of PPP1R2 alters activity of AURKA and PP1 and their phosphorylation state at the centrosome.

Fig1. PP1, PPP1R2, pR2, and AURKA are localized at the midbody.

Fig2. PPP1R2 mutant overexpression increased midbody length.

Case Study 2: Jason E Swain, 2007

Phosphorylation of histone H3 at specific residues is thought to regulate chromatin condensation. Therefore, researchers examined changes in histone H3 phosphorylation during oocyte meiosis and the potential regulation by protein PPPs. Western blot and immunocytochemical analysis revealed histone H3 phosphorylation changed during mouse oocyte meiosis, with changes in chromatin condensation. To determine whether OA-induced aberrations in chromatin condensation were due to alterations in levels of histone H3 phosphorylation, they assessed phosphorylation of Ser10 and Ser28 residues following PPP inhibition. Additionally, Western blot and immunocytochemistry confirmed presence of the PPP1C regulatory inhibitor subunit 2 (PPP1R2) in oocytes at condensed chromatin during meiosis and indicated a change in PPP1R2 phosphorylation. Inhibition of oocyte glycogen synthase kinase 3 (GSK3) appeared to regulate phosphorylation of PPP1R2. These data suggest that GSK3 inhibition results in aberrant chromatin condensation and appears to regulate phosphorylation of PPP1R2.

Fig3. ICC confirmed PPP1R2 presence and demonstrated PPP1R2 localized to condensed chromatin in MI and MII stage oocytes.

Fig4. Representative Western blot of PPP1R2 following inhibition of oocyte GSK3 via treatment.

PPP1R2 has several biochemical functions, for example, 3-oxo-5-alpha-steroid 4-dehydrogenase activity,oxidoreductase activity, acting on the CH-CH group of donors. Some of the functions are cooperated with other proteins, some of the functions could acted by PPP1R2 itself. We selected most functions PPP1R2 had, and list some proteins which have the same functions with PPP1R2. You can find most of the proteins on our site.

PPP1R2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PPP1R2 here. Most of them are supplied by our site. Hope this information will be useful for your research of PPP1R2.

PPP1CC;GSK3B;PPP1CA;LMTK2;TINF2;MYC;PPP1CB;Ppp1r10;Cep72;PPP1CC