PRKAR2B explained

cAMP-dependent protein kinase type II-beta regulatory subunit is an enzyme that in humans is encoded by the PRKAR2B gene.^{[1] [2]}

Function

cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase (PKA), which transduces the signal through phosphorylation of different target proteins. The inactive holoenzyme of PKA is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits of PKA have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. This subunit has been shown to interact with and suppress the transcriptional activity of the cAMP responsive element binding protein 1 (CREB1) in activated T cells. Knockout studies in mice suggest that this subunit may play an important role in regulating energy balance and adiposity. The studies also suggest that this subunit may mediate the gene induction and cataleptic behavior induced by haloperidol.

Interactions

PRKAR2B has been shown to interact with AKAP11 in an advanced Stage.^[3]

Further reading

• Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L . Will diverse Tat interactions lead to novel antiretroviral drug targets? . Current Drug Targets . 7 . 12 . 1595–606 . Dec 2006 . 17168834 . 10.2174/138945006779025338 .
• Luo Z, Singh IS, Fujihira T, Erlichman J . Characterization of a minimal promoter element required for transcription of the mouse type II beta regulatory subunit (RII beta) of cAMP-dependent protein kinase . The Journal of Biological Chemistry . 267 . 34 . 24738–47 . Dec 1992 . 10.1016/S0021-9258(18)35826-5 . 1332964 . free .
• Rios RM, Celati C, Lohmann SM, Bornens M, Keryer G . Identification of a high affinity binding protein for the regulatory subunit RII beta of cAMP-dependent protein kinase in Golgi enriched membranes of human lymphoblasts . The EMBO Journal . 11 . 5 . 1723–31 . May 1992 . 1582408 . 556630 . 10.1002/j.1460-2075.1992.tb05224.x.
• Tortora G, Clair T, Cho-Chung YS . An antisense oligodeoxynucleotide targeted against the type II beta regulatory subunit mRNA of protein kinase inhibits cAMP-induced differentiation in HL-60 leukemia cells without affecting phorbol ester effects . Proceedings of the National Academy of Sciences of the United States of America . 87 . 2 . 705–8 . Jan 1990 . 1689049 . 53334 . 10.1073/pnas.87.2.705 . 1990PNAS...87..705T . free .
• Hofmann B, Nishanian P, Baldwin RL, Insixiengmay P, Nel A, Fahey JL . HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism . Journal of Immunology . 145 . 11 . 3699–705 . Dec 1990 . 10.4049/jimmunol.145.11.3699 . 1978848 . free .
• Levy FO, Oyen O, Sandberg M, Taskén K, Eskild W, Hansson V, Jahnsen T . Molecular cloning, complementary deoxyribonucleic acid structure and predicted full-length amino acid sequence of the hormone-inducible regulatory subunit of 3'-5'-cyclic adenosine monophosphate-dependent protein kinase from human testis . Molecular Endocrinology . 2 . 12 . 1364–73 . Dec 1988 . 2851102 . 10.1210/mend-2-12-1364 . free .
• Scambler P, Oyen O, Wainwright B, Farrall M, Law HY, Estivill X, Sandberg M, Williamson R, Jahnsen T . Exclusion of catalytic and regulatory subunits of cAMP-dependent protein kinase as candidate genes for the defect causing cystic fibrosis . American Journal of Human Genetics . 41 . 5 . 925–32 . Nov 1987 . 3479018 . 1684338 .
• Wainwright B, Lench N, Davies K, Scambler P, Kruyer H, Williamson R, Jahnsen T, Farrall M . A human regulatory subunit of type II cAMP-dependent protein kinase localized by its linkage relationship to several cloned chromosome 7q markers . Cytogenetics and Cell Genetics . 45 . 3–4 . 237–9 . 1988 . 3691190 . 10.1159/000132461 .
• Budillon A, Cereseto A, Kondrashin A, Nesterova M, Merlo G, Clair T, Cho-Chung YS . Point mutation of the autophosphorylation site or in the nuclear location signal causes protein kinase A RII beta regulatory subunit to lose its ability to revert transformed fibroblasts . Proceedings of the National Academy of Sciences of the United States of America . 92 . 23 . 10634–8 . Nov 1995 . 7479855 . 40666 . 10.1073/pnas.92.23.10634 . 1995PNAS...9210634B . free .
• Hofmann B, Nishanian P, Nguyen T, Insixiengmay P, Fahey JL . Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes . Proceedings of the National Academy of Sciences of the United States of America . 90 . 14 . 6676–80 . Jul 1993 . 7688126 . 46995 . 10.1073/pnas.90.14.6676 . 1993PNAS...90.6676H . free .
• Berg JP, Ree AH, Sandvik JA, Taskén K, Landmark BF, Torjesen PA, Haug E . 1,25-dihydroxyvitamin D3 alters the effect of cAMP in thyroid cells by increasing the regulatory subunit type II beta of the cAMP-dependent protein kinase . The Journal of Biological Chemistry . 269 . 51 . 32233–8 . Dec 1994 . 10.1016/S0021-9258(18)31626-0 . 7798223 . free .
• Li Y, Rubin CS . Mutagenesis of the regulatory subunit (RII beta) of cAMP-dependent protein kinase II beta reveals hydrophobic amino acids that are essential for RII beta dimerization and/or anchoring RII beta to the cytoskeleton . The Journal of Biological Chemistry . 270 . 4 . 1935–44 . Jan 1995 . 7829531 . 10.1074/jbc.270.4.1935 . free .
• Hofmann B, Nishanian P, Fan J, Nguyen T, Fahey JL . HIV Gag p17 protein impairs proliferation of normal lymphocytes in vitro . AIDS . 8 . 7 . 1016–7 . Jul 1994 . 7946090 . 10.1097/00002030-199407000-00025 .
• Glantz SB, Li Y, Rubin CS . Characterization of distinct tethering and intracellular targeting domains in AKAP75, a protein that links cAMP-dependent protein kinase II beta to the cytoskeleton . The Journal of Biological Chemistry . 268 . 17 . 12796–804 . Jun 1993 . 10.1016/S0021-9258(18)31458-3 . 8509414 . free .
• Keryer G, Luo Z, Cavadore JC, Erlichman J, Bornens M . Phosphorylation of the regulatory subunit of type II beta cAMP-dependent protein kinase by cyclin B/p34cdc2 kinase impairs its binding to microtubule-associated protein 2 . Proceedings of the National Academy of Sciences of the United States of America . 90 . 12 . 5418–22 . Jun 1993 . 8516283 . 46731 . 10.1073/pnas.90.12.5418 . 1993PNAS...90.5418K . free .
• Swingler S, Gallay P, Camaur D, Song J, Abo A, Trono D . The Nef protein of human immunodeficiency virus type 1 enhances serine phosphorylation of the viral matrix . Journal of Virology . 71 . 6 . 4372–7 . Jun 1997 . 9151826 . 191654 . 10.1128/JVI.71.6.4372-4377.1997.
• Chen P, Mayne M, Power C, Nath A . The Tat protein of HIV-1 induces tumor necrosis factor-alpha production. Implications for HIV-1-associated neurological diseases . The Journal of Biological Chemistry . 272 . 36 . 22385–8 . Sep 1997 . 9278385 . 10.1074/jbc.272.36.22385 . free .
• Huang LJ, Durick K, Weiner JA, Chun J, Taylor SS . D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain . Proceedings of the National Academy of Sciences of the United States of America . 94 . 21 . 11184–9 . Oct 1997 . 9326583 . 23409 . 10.1073/pnas.94.21.11184 . 1997PNAS...9411184J . free .
• Zidovetzki R, Wang JL, Chen P, Jeyaseelan R, Hofman F . Human immunodeficiency virus Tat protein induces interleukin 6 mRNA expression in human brain endothelial cells via protein kinase C- and cAMP-dependent protein kinase pathways . AIDS Research and Human Retroviruses . 14 . 10 . 825–33 . Jul 1998 . 9671211 . 10.1089/aid.1998.14.825 .

Notes and References

1. Solberg R, Sistonen P, Träskelin AL, Bérubé D, Simard J, Krajci P, Jahnsen T, de la Chapelle A . Mapping of the regulatory subunits RI beta and RII beta of cAMP-dependent protein kinase genes on human chromosome 7 . Genomics . 14 . 1 . 63–9 . Sep 1992 . 1358799 . 10.1016/S0888-7543(05)80284-8 .
2. Web site: Entrez Gene: PRKAR2B protein kinase, cAMP-dependent, regulatory, type II, beta.
3. Reinton N, Collas P, Haugen TB, Skâlhegg BS, Hansson V, Jahnsen T, Taskén K . Localization of a novel human A-kinase-anchoring protein, hAKAP220, during spermatogenesis . Developmental Biology . 223 . 1 . 194–204 . Jul 2000 . 10864471 . 10.1006/dbio.2000.9725 . free .