PRKAR2A

Protein kinase, cAMP-dependent, regulatory, type II, alpha

PDB rendering based on 1l6e.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsPRKAR2A ; PKR2; PRKAR2
External IDsOMIM: 176910 MGI: 108025 HomoloGene: 3064 IUPHAR: 1474 ChEMBL: 2221 GeneCards: PRKAR2A Gene
EC number2.7.11.1
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez557619087
EnsemblENSG00000114302ENSMUSG00000032601
UniProtP13861Q8K1M3
RefSeq (mRNA)NM_004157NM_008924
RefSeq (protein)NP_004148NP_032950
Location (UCSC)Chr 3:
48.74 – 48.85 Mb		Chr 9:
108.69 – 108.75 Mb
PubMed search

cAMP-dependent protein kinase type II-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR2A gene.[1]

cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent Protein Kinase, more commonly called Protein Kinase A (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. It may interact with various A-kinase anchoring proteins (AKAPs) and determine the subcellular localization of PKA. This subunit has been shown to regulate protein transport from endosomes to the Golgi apparatus and further to the endoplasmic reticulum (ER).[2]

Interactions

PRKAR2A has been shown to interact with AKAP2,[3][4] AKAP1,[5][6] AKAP11,[3][7][8] AKAP8,[9][10] ARFGEF2,[11] AKAP9,[3][12] GSK3B,[7] AKAP3,[13][14] RUNX1T1,[15] AKAP13,[3][16] CBFA2T3[17] and PDE4A.[18]

See also

References

  1. ↑ Tasken K, Naylor SL, Solberg R, Jahnsen T (October 1998). "Mapping of the gene encoding the regulatory subunit RII alpha of cAMP-dependent protein kinase (locus PRKAR2A) to human chromosome region 3p21.3-p21.2". Genomics 50 (3): 378–81. doi:10.1006/geno.1998.5326. PMID 9676433.
  2. ↑ "Entrez Gene: PRKAR2A protein kinase, cAMP-dependent, regulatory, type II, alpha".
  3. ↑ 3.0 3.1 3.2 3.3 Alto, Neal M; Soderling Scott H; Hoshi Naoto; Langeberg Lorene K; Fayos Rosa; Jennings Patricia A; Scott John D (April 2003). "Bioinformatic design of A-kinase anchoring protein-in silico: a potent and selective peptide antagonist of type II protein kinase A anchoring". Proc. Natl. Acad. Sci. U.S.A. (United States) 100 (8): 4445–50. doi:10.1073/pnas.0330734100. ISSN 0027-8424. PMC 153575. PMID 12672969.
  4. ↑ Dong, F; Feldmesser M; Casadevall A; Rubin C S (March 1998). "Molecular characterization of a cDNA that encodes six isoforms of a novel murine A kinase anchor protein". J. Biol. Chem. (UNITED STATES) 273 (11): 6533–41. doi:10.1074/jbc.273.11.6533. ISSN 0021-9258. PMID 9497389.
  5. ↑ Herberg, F W; Maleszka A; Eide T; Vossebein L; Tasken K (April 2000). "Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding". J. Mol. Biol. (ENGLAND) 298 (2): 329–39. doi:10.1006/jmbi.2000.3662. ISSN 0022-2836. PMID 10764601.
  6. ↑ Kapiloff, M S; Schillace R V; Westphal A M; Scott J D (August 1999). "mAKAP: an A-kinase anchoring protein targeted to the nuclear membrane of differentiated myocytes". J. Cell. Sci. (ENGLAND) 112 (16): 2725–36. ISSN 0021-9533. PMID 10413680.
  7. ↑ 7.0 7.1 Tanji, Chie; Yamamoto Hideki; Yorioka Noriaki; Kohno Nobuoki; Kikuchi Kunimi; Kikuchi Akira (October 2002). "A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta". J. Biol. Chem. (United States) 277 (40): 36955–61. doi:10.1074/jbc.M206210200. ISSN 0021-9258. PMID 12147701.
  8. ↑ Lester, L B; Coghlan V M; Nauert B; Scott J D (April 1996). "Cloning and characterization of a novel A-kinase anchoring protein. AKAP 220, association with testicular peroxisomes". J. Biol. Chem. (UNITED STATES) 271 (16): 9460–5. doi:10.1074/jbc.271.16.9460. ISSN 0021-9258. PMID 8621616.
  9. ↑ Eide, T; Coghlan V, Orstavik S, Holsve C, Solberg R, Skâlhegg B S, Lamb N J, Langeberg L, Fernandez A, Scott J D, Jahnsen T, Taskén K (February 1998). "Molecular cloning, chromosomal localization, and cell cycle-dependent subcellular distribution of the A-kinase anchoring protein, AKAP95". Exp. Cell Res. (UNITED STATES) 238 (2): 305–16. doi:10.1006/excr.1997.3855. ISSN 0014-4827. PMID 9473338.
  10. ↑ Collas, P; Le Guellec K; Taskén K (December 1999). "The A-kinase-anchoring protein AKAP95 is a multivalent protein with a key role in chromatin condensation at mitosis". J. Cell Biol. (UNITED STATES) 147 (6): 1167–80. doi:10.1083/jcb.147.6.1167. ISSN 0021-9525. PMC 2168084. PMID 10601332.
  11. ↑ Li, Hewang; Adamik Ronald, Pacheco-Rodriguez Gustavo, Moss Joel, Vaughan Martha (February 2003). "Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2)". Proc. Natl. Acad. Sci. U.S.A. (United States) 100 (4): 1627–32. doi:10.1073/pnas.0337678100. ISSN 0027-8424. PMC 149883. PMID 12571360.
  12. ↑ Takahashi, M; Shibata H; Shimakawa M; Miyamoto M; Mukai H; Ono Y (June 1999). "Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus". J. Biol. Chem. (UNITED STATES) 274 (24): 17267–74. doi:10.1074/jbc.274.24.17267. ISSN 0021-9258. PMID 10358086.
  13. ↑ Vijayaraghavan, S; Liberty G A; Mohan J; Winfrey V P; Olson G E; Carr D W (May 1999). "Isolation and molecular characterization of AKAP110, a novel, sperm-specific protein kinase A-anchoring protein". Mol. Endocrinol. (UNITED STATES) 13 (5): 705–17. doi:10.1210/mend.13.5.0278. ISSN 0888-8809. PMID 10319321.
  14. ↑ Carr, D W; Fujita A; Stentz C L; Liberty G A; Olson G E; Narumiya S (May 2001). "Identification of sperm-specific proteins that interact with A-kinase anchoring proteins in a manner similar to the type II regulatory subunit of PKA". J. Biol. Chem. (United States) 276 (20): 17332–8. doi:10.1074/jbc.M011252200. ISSN 0021-9258. PMID 11278869.
  15. ↑ Fukuyama, T; Sueoka E; Sugio Y; Otsuka T; Niho Y; Akagi K; Kozu T (September 2001). "MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". Oncogene (England) 20 (43): 6225–32. doi:10.1038/sj.onc.1204794. ISSN 0950-9232. PMID 11593431.
  16. ↑ Carr, D W; Hausken Z E; Fraser I D; Stofko-Hahn R E; Scott J D (July 1992). "Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain". J. Biol. Chem. (UNITED STATES) 267 (19): 13376–82. ISSN 0021-9258. PMID 1618839.
  17. ↑ Schillace, Robynn V; Andrews Sarah F; Liberty Greg A; Davey Michael P; Carr Daniel W (February 2002). "Identification and characterization of myeloid translocation gene 16b as a novel a kinase anchoring protein in T lymphocytes". J. Immunol. (United States) 168 (4): 1590–9. doi:10.4049/jimmunol.168.4.1590. ISSN 0022-1767. PMID 11823486.
  18. ↑ Dodge, K L; Khouangsathiene S; Kapiloff M S; Mouton R; Hill E V; Houslay M D; Langeberg L K; Scott J D (April 2001). "mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module". EMBO J. (England) 20 (8): 1921–30. doi:10.1093/emboj/20.8.1921. ISSN 0261-4189. PMC 125429. PMID 11296225.

Further reading

  • Cho-Chung YS, Nesterova MV (2006). "Tumor reversion: protein kinase A isozyme switching.". Ann. N. Y. Acad. Sci. 1058: 76–86. doi:10.1196/annals.1359.014. PMID 16394127.
  • Harrich D; McMillan N; Munoz L et al. (2007). "Will diverse Tat interactions lead to novel antiretroviral drug targets?". Current drug targets 7 (12): 1595–606. doi:10.2174/138945006779025338. PMID 17168834.
  • Skålhegg BS; Landmark B; Foss KB et al. (1992). "Identification, purification, and characterization of subunits of cAMP-dependent protein kinase in human testis. Reverse mobilities of human RII alpha and RII beta on sodium dodecyl sulfate-polyacrylamide gel electrophoresis compared with rat and bovine RIIs". J. Biol. Chem. 267 (8): 5374–9. PMID 1544918.
  • Carr DW; Hausken ZE; Fraser ID et al. (1992). "Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain". J. Biol. Chem. 267 (19): 13376–82. PMID 1618839.
  • Hofmann B; Nishanian P; Baldwin RL et al. (1991). "HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism". J. Immunol. 145 (11): 3699–705. PMID 1978848.
  • Scott JD; Stofko RE; McDonald JR et al. (1991). "Type II regulatory subunit dimerization determines the subcellular localization of the cAMP-dependent protein kinase". J. Biol. Chem. 265 (35): 21561–6. PMID 2147685.
  • Oyen O; Myklebust F; Scott JD et al. (1989). "Human testis cDNA for the regulatory subunit RII alpha of cAMP-dependent protein kinase encodes an alternate amino-terminal region". FEBS Lett. 246 (1–2): 57–64. doi:10.1016/0014-5793(89)80253-4. PMID 2540040.
  • Obar RA, Dingus J, Bayley H, Vallee RB (1990). "The RII subunit of cAMP-dependent protein kinase binds to a common amino-terminal domain in microtubule-associated proteins 2A, 2B, and 2C". Neuron 3 (5): 639–45. doi:10.1016/0896-6273(89)90274-2. PMID 2561973.
  • Rubino HM, Dammerman M, Shafit-Zagardo B, Erlichman J (1990). "Localization and characterization of the binding site for the regulatory subunit of type II cAMP-dependent protein kinase on MAP2". Neuron 3 (5): 631–8. doi:10.1016/0896-6273(89)90273-0. PMID 2701845.
  • Hemmings BA; Aitken A; Cohen P et al. (1983). "Phosphorylation of the type-II regulatory subunit of cyclic-AMP-dependent protein kinase by glycogen synthase kinase 3 and glycogen synthase kinase 5". Eur. J. Biochem. 127 (3): 473–81. doi:10.1111/j.1432-1033.1982.tb06896.x. PMID 6293815.
  • Hofmann B; Nishanian P; Nguyen T et al. (1993). "Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes". Proc. Natl. Acad. Sci. U.S.A. 90 (14): 6676–80. doi:10.1073/pnas.90.14.6676. PMC 46995. PMID 7688126.
  • Pariset C, Weinman S (1995). "Differential localization of two isoforms of the regulatory subunit RII alpha of cAMP-dependent protein kinase in human sperm: biochemical and cytochemical study". Mol. Reprod. Dev. 39 (4): 415–22. doi:10.1002/mrd.1080390410. PMID 7893490.
  • Cheley S; Panchal RG; Carr DW et al. (1994). "Type II regulatory subunits of cAMP-dependent protein kinase and their binding proteins in the nervous system of Aplysia californica". J. Biol. Chem. 269 (4): 2911–20. PMID 7905481.
  • Hausken ZE; Coghlan VM; Hastings CA et al. (1994). "Type II regulatory subunit (RII) of the cAMP-dependent protein kinase interaction with A-kinase anchor proteins requires isoleucines 3 and 5". J. Biol. Chem. 269 (39): 24245–51. PMID 7929081.
  • Hofmann B; Nishanian P; Fan J et al. (1994). "HIV Gag p17 protein impairs proliferation of normal lymphocytes in vitro". AIDS 8 (7): 1016–7. doi:10.1097/00002030-199407000-00025. PMID 7946090.
  • Beebe SJ, Salomonsky P, Holroyd C, Becker D (1994). "Differential expression of cyclic AMP-dependent protein kinase isozymes in normal human melanocytes and malignant melanomas". Cell Growth Differ. 4 (12): 1005–12. PMID 8117614.
  • Coghlan VM; Langeberg LK; Fernandez A et al. (1994). "Cloning and characterization of AKAP 95, a nuclear protein that associates with the regulatory subunit of type II cAMP-dependent protein kinase". J. Biol. Chem. 269 (10): 7658–65. PMID 8125992.
  • Lester LB, Coghlan VM, Nauert B, Scott JD (1996). "Cloning and characterization of a novel A-kinase anchoring protein. AKAP 220, association with testicular peroxisomes". J. Biol. Chem. 271 (16): 9460–5. doi:10.1074/jbc.271.16.9460. PMID 8621616.
  • Foss KB; Solberg R; Simard J et al. (1997). "Molecular cloning, upstream sequence and promoter studies of the human gene for the regulatory subunit RII alpha of cAMP-dependent protein kinase". Biochim. Biophys. Acta 1350 (1): 98–108. doi:10.1016/S0167-4781(96)00152-2. PMID 9003463.
  • Dransfield DT; Bradford AJ; Smith J et al. (1997). "Ezrin is a cyclic AMP-dependent protein kinase anchoring protein". EMBO J. 16 (1): 35–43. doi:10.1093/emboj/16.1.35. PMC 1169611. PMID 9009265.