PPP2R4 explained

Serine/threonine-protein phosphatase 2A regulatory subunit B is an enzyme that in humans is encoded by the PPP2R4 gene.^{[1] [2]}

Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms.^[2]

Interactions

PPP2R4 has been shown to interact with PPP2R3A,^[3] CCNG1^[4] and Janus kinase 2.^[5]

Further reading

• Andersen JL, Planelles V . The role of Vpr in HIV-1 pathogenesis. . Curr. HIV Res. . 3 . 1 . 43–51 . 2005 . 15638722 . 10.2174/1570162052772988 .
• Le Rouzic E, Benichou S . The Vpr protein from HIV-1: distinct roles along the viral life cycle. . Retrovirology . 2 . 11 . 2006 . 15725353 . 10.1186/1742-4690-2-11 . 554975 . free .
• Zhao RY, Elder RT . Viral infections and cell cycle G2/M regulation. . Cell Res. . 15 . 3 . 143–9 . 2005 . 15780175 . 10.1038/sj.cr.7290279 . free .
• Zhao RY, Bukrinsky M, Elder RT . HIV-1 viral protein R (Vpr) & host cellular responses. . Indian J. Med. Res. . 121 . 4 . 270–86 . 2005 . 15817944 .
• Soprano KJ, Purev E, Vuocolo S, Soprano DR . Rb2/p130 and protein phosphatase 2A: key mediators of ovarian carcinoma cell growth suppression by all-trans retinoic acid. . Oncogene . 25 . 38 . 5315–25 . 2006 . 16936753 . 10.1038/sj.onc.1209679 . free .
• Jakes S, Mellgren RL, Schlender KK . Isolation and characterization of an inhibitor-sensitive and a polycation-stimulated protein phosphatase from rat liver nuclei. . Biochim. Biophys. Acta . 888 . 1 . 135–42 . 1986 . 3017441 . 10.1016/0167-4889(86)90079-0 .
• Turowski P, Fernandez A, Favre B, etal . Differential methylation and altered conformation of cytoplasmic and nuclear forms of protein phosphatase 2A during cell cycle progression. . J. Cell Biol. . 129 . 2 . 397–410 . 1995 . 7721943 . 10.1083/jcb.129.2.397 . 2199911 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Cayla X, Van Hoof C, Bosch M, etal . Molecular cloning, expression, and characterization of PTPA, a protein that activates the tyrosyl phosphatase activity of protein phosphatase 2A. . J. Biol. Chem. . 269 . 22 . 15668–75 . 1994 . 10.1016/S0021-9258(17)40733-2 . 8195217 . free .
• Okamoto K, Kamibayashi C, Serrano M, etal . p53-dependent association between cyclin G and the B' subunit of protein phosphatase 2A. . Mol. Cell. Biol. . 16 . 11 . 6593–602 . 1996 . 8887688 . 10.1128/mcb.16.11.6593. 231661 .
• Tung HY, De Rocquigny H, Zhao LJ, etal . Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr. . FEBS Lett. . 401 . 2–3 . 197–201 . 1997 . 9013886 . 10.1016/S0014-5793(96)01470-6 . 23293768 . free .
• Hériché JK, Lebrin F, Rabilloud T, etal . Regulation of protein phosphatase 2A by direct interaction with casein kinase 2alpha. . Science . 276 . 5314 . 952–5 . 1997 . 9139659 . 10.1126/science.276.5314.952 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Ruediger R, Brewis N, Ohst K, Walter G . Increasing the ratio of PP2A core enzyme to holoenzyme inhibits Tat-stimulated HIV-1 transcription and virus production. . Virology . 238 . 2 . 432–43 . 1998 . 9400615 . 10.1006/viro.1997.8873 . free .
• Ogris E, Du X, Nelson KC, etal . A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A. . J. Biol. Chem. . 274 . 20 . 14382–91 . 1999 . 10318862 . 10.1074/jbc.274.20.14382 . 3503312. free .
• Janssens V, Van Hoof C, De Baere I, etal . Functional analysis of the promoter region of the human phosphotyrosine phosphatase activator gene: Yin Yang 1 is essential for core promoter activity. . Biochem. J. . 344 . 3. 755–63 . 2000 . 10585862 . 10.1042/0264-6021:3440755. 1220697 .
• Janssens V, van Hoof C, Martens E, etal . Identification and characterization of alternative splice products encoded by the human phosphotyrosyl phosphatase activator gene. . Eur. J. Biochem. . 267 . 14 . 4406–13 . 2000 . 10880964 . 10.1046/j.1432-1327.2000.01486.x . free .
• Elder RT, Yu M, Chen M, etal . HIV-1 Vpr induces cell cycle G2 arrest in fission yeast (Schizosaccharomyces pombe) through a pathway involving regulatory and catalytic subunits of PP2A and acting on both Wee1 and Cdc25. . Virology . 287 . 2 . 359–70 . 2001 . 11531413 . 10.1006/viro.2001.1007 . free .

Notes and References

1. Van Hoof C, Aly MS, Garcia A, Cayla X, Cassiman JJ, Merlevede W, Goris J . Structure and chromosomal localization of the human gene of the phosphotyrosyl phosphatase activator (PTPA) of protein phosphatase 2A . Genomics . 28 . 2 . 261–72 . Feb 1996 . 8530035 . 10.1006/geno.1995.1140 .
2. Web site: Entrez Gene: PPP2R4 protein phosphatase 2A activator, regulatory subunit 4.
3. Davis . Anthony J . Yan Zhen . Martinez Bobbie . Mumby Marc C . Jun 2008 . Protein phosphatase 2A is targeted to cell division control protein 6 by a calcium-binding regulatory subunit . J. Biol. Chem. . 283 . 23 . 16104–14 . United States. 0021-9258. 18397887 . 10.1074/jbc.M710313200 . 2414307 . free .
4. Okamoto . K . Kamibayashi C . Serrano M . Prives C . Mumby M C . Beach D . Nov 1996 . p53-dependent association between cyclin G and the B' subunit of protein phosphatase 2A . Mol. Cell. Biol. . 16 . 11 . 6593–602 . UNITED STATES. 0270-7306. 8887688 . 231661 . 10.1128/mcb.16.11.6593 .
5. 10.1006/bbrc.1996.1023 . Fuhrer . D K . Yang Y C . Jul 1996 . Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11 . Biochem. Biophys. Res. Commun. . 224 . 2 . 289–96 . UNITED STATES. 0006-291X. 8702385 .