PPP2R5A explained

Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform is an enzyme that in humans is encoded by the PPP2R5A gene.^[1]

Function

The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an alpha isoform of the regulatory subunit B56 subfamily.^[2]

Interactions

PPP2R5A has been shown to interact with:

• AXIN1,^[3]
• CTLA-4,^[4]
• PPP2CA,
• PPP2R1A,
• PPP2R1B,^{[5] [6] [7] [8]} and
• PPP2R5C^[8]

Further reading

• Andersen JL, Planelles V . The role of Vpr in HIV-1 pathogenesis . Current HIV Research . 3 . 1 . 43–51 . Jan 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 . 554975 . 10.1186/1742-4690-2-11 . free .
• Zhao RY, Elder RT . Viral infections and cell cycle G2/M regulation . Cell Research . 15 . 3 . 143–9 . Mar 2005 . 15780175 . 10.1038/sj.cr.7290279 . free .
• Zhao RY, Bukrinsky M, Elder RT . HIV-1 viral protein R (Vpr) & host cellular responses . The Indian Journal of Medical Research . 121 . 4 . 270–86 . Apr 2005 . 15817944 .
• Zolnierowicz S, Van Hoof C, Andjelković N, Cron P, Stevens I, Merlevede W, Goris J, Hemmings BA . The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits . The Biochemical Journal . 317 . 1 . 187–94 . Jul 1996 . 8694763 . 1217462 . 10.1042/bj3170187.
• Fuhrer DK, Yang YC . Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11 . Biochemical and Biophysical Research Communications . 224 . 2 . 289–96 . Jul 1996 . 8702385 . 10.1006/bbrc.1996.1023 .
• McCright B, Rivers AM, Audlin S, Virshup DM . The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm . The Journal of Biological Chemistry . 271 . 36 . 22081–9 . Sep 1996 . 8703017 . 10.1074/jbc.271.36.22081 . free .
• McCright B, Brothman AR, Virshup DM . Assignment of human protein phosphatase 2A regulatory subunit genes b56alpha, b56beta, b56gamma, b56delta, and b56epsilon (PPP2R5A-PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2 --> p12 . Genomics . 36 . 1 . 168–70 . Aug 1996 . 8812429 . 10.1006/geno.1996.0438 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Tung HY, De Rocquigny H, Zhao LJ, Cayla X, Roques BP, Ozon R . Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr . FEBS Letters . 401 . 2–3 . 197–201 . Jan 1997 . 9013886 . 10.1016/S0014-5793(96)01470-6 . free .
• 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 . Nov 1997 . 9400615 . 10.1006/viro.1997.8873 . free .
• Ruediger R, Fields K, Walter G . Binding specificity of protein phosphatase 2A core enzyme for regulatory B subunits and T antigens . Journal of Virology . 73 . 1 . 839–42 . Jan 1999 . 10.1128/JVI.73.1.839-842.1999 . 9847399 . 103900 .
• Seeling JM, Miller JR, Gil R, Moon RT, White R, Virshup DM . Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A . Science . 283 . 5410 . 2089–91 . Mar 1999 . 10092233 . 10.1126/science.283.5410.2089 .
• Xu Z, Williams BR . The B56alpha regulatory subunit of protein phosphatase 2A is a target for regulation by double-stranded RNA-dependent protein kinase PKR . Molecular and Cellular Biology . 20 . 14 . 5285–99 . Jul 2000 . 10866685 . 85978 . 10.1128/MCB.20.14.5285-5299.2000 .
• Fleming I, Fisslthaler B, Dimmeler S, Kemp BE, Busse R . Phosphorylation of Thr(495) regulates Ca(2+)/calmodulin-dependent endothelial nitric oxide synthase activity . Circulation Research . 88 . 11 . E68–75 . Jun 2001 . 11397791 . 10.1161/hh1101.092677 . 86348254 .
• Elder RT, Yu M, Chen M, Zhu X, Yanagida M, Zhao Y . 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 . Sep 2001 . 11531413 . 10.1006/viro.2001.1007 . free .
• Galea MA, Eleftheriou A, Henderson BR . ARM domain-dependent nuclear import of adenomatous polyposis coli protein is stimulated by the B56 alpha subunit of protein phosphatase 2A . The Journal of Biological Chemistry . 276 . 49 . 45833–9 . Dec 2001 . 11585828 . 10.1074/jbc.M107149200 . free .
• Li X, Virshup DM . Two conserved domains in regulatory B subunits mediate binding to the A subunit of protein phosphatase 2A . European Journal of Biochemistry . 269 . 2 . 546–52 . Jan 2002 . 11856313 . 10.1046/j.0014-2956.2001.02680.x . free .

Notes and References

1. McCright B, Virshup DM . Identification of a new family of protein phosphatase 2A regulatory subunits . The Journal of Biological Chemistry . 270 . 44 . 26123–8 . Nov 1995 . 7592815 . 10.1074/jbc.270.44.26123 . free .
2. Web site: Entrez Gene: PPP2R5A protein phosphatase 2, regulatory subunit B', alpha isoform.
3. Yamamoto H, Hinoi T, Michiue T, Fukui A, Usui H, Janssens V, Van Hoof C, Goris J, Asashima M, Kikuchi A . Inhibition of the Wnt signaling pathway by the PR61 subunit of protein phosphatase 2A . The Journal of Biological Chemistry . 276 . 29 . 26875–82 . Jul 2001 . 11297546 . 10.1074/jbc.M100443200 . free .
4. Baroja ML, Vijayakrishnan L, Bettelli E, Darlington PJ, Chau TA, Ling V, Collins M, Carreno BM, Madrenas J, Kuchroo VK . Inhibition of CTLA-4 function by the regulatory subunit of serine/threonine phosphatase 2A . Journal of Immunology . 168 . 10 . 5070–8 . May 2002 . 11994459 . 10.4049/jimmunol.168.10.5070. free .
5. Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, Chaudhry S, Chen GI, Sicheri F, Nesvizhskii AI, Aebersold R, Raught B, Gingras AC . A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein . Molecular & Cellular Proteomics . 8 . 1 . 157–71 . Jan 2009 . 18782753 . 2621004 . 10.1074/mcp.M800266-MCP200 . free .
6. Zhou J, Pham HT, Ruediger R, Walter G . Characterization of the Aalpha and Abeta subunit isoforms of protein phosphatase 2A: differences in expression, subunit interaction, and evolution . The Biochemical Journal . 369 . Pt 2 . 387–98 . Jan 2003 . 12370081 . 1223084 . 10.1042/BJ20021244 .
7. McCright B, Rivers AM, Audlin S, Virshup DM . The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm . The Journal of Biological Chemistry . 271 . 36 . 22081–9 . Sep 1996 . 8703017 . 10.1074/jbc.271.36.22081. free .
8. Strack S, Ruediger R, Walter G, Dagda RK, Barwacz CA, Cribbs JT . Protein phosphatase 2A holoenzyme assembly: identification of contacts between B-family regulatory and scaffolding A subunits . The Journal of Biological Chemistry . 277 . 23 . 20750–5 . Jun 2002 . 11929880 . 10.1074/jbc.M202992200. free .