Genomes and Genes
Gene Symbol: Prkar2a
Description: protein kinase, cAMP dependent regulatory, type II alpha
Alias: 1110061A24Rik, AI317181, AI836829, RII(alpha), cAMP-dependent protein kinase type II-alpha regulatory subunit
- Imaizumi Scherrer T, Faust D, Benichou J, Hellio R, Weiss M. Accumulation in fetal muscle and localization to the neuromuscular junction of cAMP-dependent protein kinase A regulatory and catalytic subunits RI alpha and C alpha. J Cell Biol. 1996;134:1241-54 pubmed..In the adult, the C alpha hybridization signal of muscle is weak and homogeneous...
- Dong F, Feldmesser M, Casadevall A, Rubin C. Molecular characterization of a cDNA that encodes six isoforms of a novel murine A kinase anchor protein. J Biol Chem. 1998;273:6533-41 pubmed
- Fukuda M, Aizawa Y. Hypothetical gene C18orf42 encodes a novel protein kinase A-binding protein. Genes Cells. 2015;20:267-80 pubmed publisher..These findings suggest that C18orf42 may be a novel PKA signaling gene that serves as an endogenous disruptor peptide for PKA-AKAP interactions. ..
- Morikis D, Roy M, Newlon M, Scott J, Jennings P. Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIalpha. Eur J Biochem. 2002;269:2040-51 pubmed..We also discuss the structural requirements necessary for the formation of a stacked (rather than intertwined) dimer, which has consequences for the orientation of the functionally important and distinct faces. ..
- Xu K, Qi H. Sperm-specific AKAP3 is a dual-specificity anchoring protein that interacts with both protein kinase a regulatory subunits via conserved N-terminal amphipathic peptides. Mol Reprod Dev. 2014;81:595-607 pubmed publisher..Thus, AKAP3 is a dual-specificity molecule that modulates PKA isotypes in a spatiotemporal manner during mouse spermatogenesis. ..
- Newlon M, Roy M, Hausken Z, Scott J, Jennings P. The A-kinase anchoring domain of type IIalpha cAMP-dependent protein kinase is highly helical. J Biol Chem. 1997;272:23637-44 pubmed..The assignments and secondary structure analysis provide the basis for analyzing the structure and dynamics of the dimerization domain both free and complexed with specific anchoring proteins. ..
- Schillace R, Andrews S, Galligan S, Burton K, Starks H, Bouwer H, et al. The role of protein kinase A anchoring via the RII alpha regulatory subunit in the murine immune system. J Immunol. 2005;174:6847-53 pubmed
- Zhong H, Sia G, Sato T, Gray N, Mao T, Khuchua Z, et al. Subcellular dynamics of type II PKA in neurons. Neuron. 2009;62:363-74 pubmed publisher..Therefore, the localization and activity-dependent translocation of type II PKA are important determinants of PKA function. ..
- Webb R, Tinworth L, Thomas G, Zaccolo M, Carroll J. Developmentally acquired PKA localisation in mouse oocytes and embryos. Dev Biol. 2008;317:36-45 pubmed publisher..RT-PCR and Western blotting revealed two candidate AKAPs that are known to be targeted to mitochondria, AKAP1 and D-AKAP2. In summary these data show a dynamic regulation of PKA localisation during oocyte and early embryo development. ..
- Yin Z, Jones G, Towns W, Zhang X, Abel E, Binkley P, et al. Heart-specific ablation of Prkar1a causes failure of heart development and myxomagenesis. Circulation. 2008;117:1414-22 pubmed publisher..These biochemical changes lead to myxoma-like changes, indicating that these mice may be a good model with which to study the formation of these tumors. ..
- Kong D, Shen Y, Liu G, Zuo S, Ji Y, Lu A, et al. PKA regulatory II? subunit is essential for PGD2-mediated resolution of inflammation. J Exp Med. 2016;213:2209-26 pubmed publisher..signaling in macrophages, whereas its activation facilitated binding of the separated PKA regulatory II? subunit (PRKAR2A) to the transmembrane domain of IFN-? receptor, suppressed JAK2-STAT1 axis-mediated M1 polarization, and promoted ..
- Patel H, Hamuro L, Chun B, Kawaraguchi Y, Quick A, Rebolledo B, et al. Disruption of protein kinase A localization using a trans-activator of transcription (TAT)-conjugated A-kinase-anchoring peptide reduces cardiac function. J Biol Chem. 2010;285:27632-40 pubmed publisher..Disruption of PKA localization with TAT-AKAD thus had negative effects on chronotropy, inotropy, and lusitropy, thereby indicating a key role for AKAP-targeted PKA in control of heart rate and contractile function. ..
- Barzi M, Berenguer J, Menendez A, Alvarez Rodriguez R, Pons S. Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base. J Cell Sci. 2010;123:62-9 pubmed publisher..Collectively, these results demonstrate that the pool of PKA localized to the cilium base of CGNP plays an essential role in the integration of Shh signal transduction. ..
- Amieux P, Howe D, Knickerbocker H, Lee D, Su T, Laszlo G, et al. Increased basal cAMP-dependent protein kinase activity inhibits the formation of mesoderm-derived structures in the developing mouse embryo. J Biol Chem. 2002;277:27294-304 pubmed..Our results demonstrate that unregulated PKA activity negatively affects growth factor-mediated mesoderm formation during early mouse development. ..
- Carlson C, Lygren B, Berge T, Hoshi N, Wong W, Tasken K, et al. Delineation of type I protein kinase A-selective signaling events using an RI anchoring disruptor. J Biol Chem. 2006;281:21535-45 pubmed..This study suggests that these processes are controlled by the type I PKA holoenzyme and that RIAD can be used as a tool to define anchored type I PKA signaling events. ..
- Rao Y, Fischer Q, Yang Y, McKnight G, LaRue A, Daw N. Reduced ocular dominance plasticity and long-term potentiation in the developing visual cortex of protein kinase A RII alpha mutant mice. Eur J Neurosci. 2004;20:837-42 pubmed..vitro and ocular dominance plasticity in vivo in the developing visual cortex were examined in mice lacking the RII alpha subunit of PKA...
- Wu J, Brown S, von Daake S, Taylor S. PKA type IIalpha holoenzyme reveals a combinatorial strategy for isoform diversity. Science. 2007;318:274-9 pubmed..This structure demonstrates the conserved and isoform-specific features of RI and RII and the importance of ATP, and also provides a new paradigm for designing isoform-specific activators or antagonists for PKA. ..
- Saloustros E, Salpea P, Qi C, Gugliotti L, Tsang K, Liu S, et al. Hematopoietic neoplasms in Prkar2a-deficient mice. J Exp Clin Cancer Res. 2015;34:143 pubmed publisher..Mice with inactivation of the Prkar2a and Prkar2b genes (coding for RIIÎ± and RIIÎ², respectively) are also viable but have not been studied for ..
- London E, Nesterova M, Sinaii N, Szarek E, Chanturiya T, Mastroyannis S, et al. Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to diet-induced obesity and glucose intolerance in mice that lack PKA regulatory subunit type II?. Endocrinology. 2014;155:3397-408 pubmed publisher..We conclude that RII? represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease. ..
- Hinke S, Navedo M, Ulman A, Whiting J, Nygren P, Tian G, et al. Anchored phosphatases modulate glucose homeostasis. EMBO J. 2012;31:3991-4004 pubmed publisher..Thus anchored signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP150 associated phosphatase activity. ..
- Ryu H, Lee J, Impey S, Ratan R, Ferrante R. Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neurons. Proc Natl Acad Sci U S A. 2005;102:13915-20 pubmed..These results suggest that the regulation of mitochondrial function via the mitochondrial PKA and CREB pathways may underlie some of the salutary effects of DFO in neurons. ..
- Dyson M, Jones J, Kowalewski M, Manna P, Alonso M, Gottesman M, et al. Mitochondrial A-kinase anchoring protein 121 binds type II protein kinase A and enhances steroidogenic acute regulatory protein-mediated steroidogenesis in MA-10 mouse leydig tumor cells. Biol Reprod. 2008;78:267-77 pubmed..This suggests that AKAP121 and PKAR2A serve to enhance steroidogenesis by directing the synthesis and activation of STAR at the mitochondria in response to cAMP. ..
- Ma Y, Pitson S, Hercus T, Murphy J, Lopez A, Woodcock J. Sphingosine activates protein kinase A type II by a novel cAMP-independent mechanism. J Biol Chem. 2005;280:26011-7 pubmed
- Mucignat Caretta C, Caretta A. Regional variations in the localization of insoluble kinase A regulatory isoforms during rodent brain development. J Chem Neuroanat. 2004;27:201-12 pubmed
- Bejarano E, Cabrera M, Vega L, Hidalgo J, Velasco A. Golgi structural stability and biogenesis depend on associated PKA activity. J Cell Sci. 2006;119:3764-75 pubmed..We conclude that protein kinase A activity plays a relevant role in the assembly and maintenance of a continuous Golgi ribbon from separated membrane stacks. ..
- Liu S, Saloustros E, Mertz E, Tsang K, Starost M, Salpea P, et al. Haploinsufficiency for either one of the type-II regulatory subunits of protein kinase A improves the bone phenotype of Prkar1a+/- mice. Hum Mol Genet. 2015;24:6080-92 pubmed publisher..activity due to an unregulated PKA catalytic subunit and increased PKA type II (PKA-II) activity mediated by the PRKAR2A and PRKAR2B subunits...
- Gold M, Lygren B, Dokurno P, Hoshi N, McConnachie G, Tasken K, et al. Molecular basis of AKAP specificity for PKA regulatory subunits. Mol Cell. 2006;24:383-95 pubmed
- Burton K, Johnson B, Hausken Z, Westenbroek R, Idzerda R, Scheuer T, et al. Type II regulatory subunits are not required for the anchoring-dependent modulation of Ca2+ channel activity by cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1997;94:11067-72 pubmed..The potentiation of the L-type Ca2+ channel in RIIalpha knockout mouse skeletal muscle suggests that, despite a lower affinity for AKAP binding, RIalpha is capable of physiologically relevant anchoring interactions. ..
- de Sousa S, Kawasaki K, Kawasaki M, Volponi A, Gomez R, Gomes C, et al. PKA regulatory subunit expression in tooth development. Gene Expr Patterns. 2014;15:46-51 pubmed publisher..aim of the present study was to assess the expression of alpha isoforms of PKA regulatory subunit (Prkar1a and Prkar2a) in mouse and human odontogenesis by in situ hybridization...
- Carr D, Fujita A, Stentz C, Liberty G, Olson G, Narumiya S. 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. 2001;276:17332-8 pubmed..These data suggest that sperm contains several proteins that bind to AKAPs in a manner similar to RII and imply that AKAPs may have additional and perhaps unique functions in spermatozoa. ..
- Burton K, Treash Osio B, Muller C, Dunphy E, McKnight G. Deletion of type IIalpha regulatory subunit delocalizes protein kinase A in mouse sperm without affecting motility or fertilization. J Biol Chem. 1999;274:24131-6 pubmed..Unexpectedly the RIIalpha mutant mice are fertile and have no significant changes in sperm motility. Our results demonstrate that the highly localized pattern of PKA seen in mature sperm is not essential for motility or fertilization. ..
- Greene R, Lloyd M, Uberti M, Nugent P, Pisano M. Patterns of cyclic AMP-dependent protein kinase gene expression during ontogeny of the murine palate. J Cell Physiol. 1995;163:431-40 pubmed..Levels of RII alpha and RII beta mRNA were highest on gestational day (GD) 12, a period characterized by pronounced palatal tissue ..
- Newlon M, Roy M, Morikis D, Hausken Z, Coghlan V, Scott J, et al. The molecular basis for protein kinase A anchoring revealed by solution NMR. Nat Struct Biol. 1999;6:222-7 pubmed..Interestingly, this same dimerization motif is present in other signaling molecules, the S100 family. Therefore, the X-type four-helix bundle may represent a conserved fold for protein-protein interactions in signal transduction. ..