Prkar2b

Summary

Gene Symbol: Prkar2b
Description: protein kinase, cAMP dependent regulatory, type II beta
Alias: AI451071, AW061005, PKARIIbeta, Pkarb2, RII(beta), cAMP-dependent protein kinase type II-beta regulatory subunit
Species: mouse
Products:     Prkar2b

Top Publications

  1. Cummings D, Brandon E, Planas J, Motamed K, Idzerda R, McKnight G. Genetically lean mice result from targeted disruption of the RII beta subunit of protein kinase A. Nature. 1996;382:622-6 pubmed
    ..The RII beta isoform is abundant in brown and white adipose tissue and brain, with limited expression elsewhere...
  2. Amieux P, Cummings D, Motamed K, Brandon E, Wailes L, Le K, et al. Compensatory regulation of RIalpha protein levels in protein kinase A mutant mice. J Biol Chem. 1997;272:3993-8 pubmed
    ..Compensation by RIalpha stabilization may represent an important biological mechanism that safeguards cells from unregulated catalytic subunit activity. ..
  3. Planas J, Cummings D, Idzerda R, McKnight G. Mutation of the RIIbeta subunit of protein kinase A differentially affects lipolysis but not gene induction in white adipose tissue. J Biol Chem. 1999;274:36281-7 pubmed
    ..We suggest that the R subunit isoform switch disrupts the subcellular localization of PKA that is required for efficient transduction of signals that modulate lipolysis but not for those that mediate gene expression. ..
  4. Schreyer S, Cummings D, McKnight G, LeBoeuf R. Mutation of the RIIbeta subunit of protein kinase A prevents diet-induced insulin resistance and dyslipidemia in mice. Diabetes. 2001;50:2555-62 pubmed
    ..Taken together, these data demonstrate that loss of RIIbeta protects mice from diet-induced obesity, insulin resistance, and dyslipidemia. ..
  5. Nolan M, Sikorski M, McKnight G. The role of uncoupling protein 1 in the metabolism and adiposity of RII beta-protein kinase A-deficient mice. Mol Endocrinol. 2004;18:2302-11 pubmed
    Mice lacking the RII beta regulatory subunit of protein kinase A exhibit a 50% reduction in white adipose tissue stores compared with wild-type littermates and are resistant to diet-induced obesity...
  6. Porcellini A, Messina S, De Gregorio G, Feliciello A, Carlucci A, Barone M, et al. The expression of the thyroid-stimulating hormone (TSH) receptor and the cAMP-dependent protein kinase RII beta regulatory subunit confers TSH-cAMP-dependent growth to mouse fibroblasts. J Biol Chem. 2003;278:40621-30 pubmed
  7. Singh I, Luo Z, Eng A, Erlichman J. Molecular cloning and characterization of the promoter region of the mouse regulatory subunit RII beta of type II cAMP-dependent protein kinase. Biochem Biophys Res Commun. 1991;178:221-6 pubmed
    ..Fusion gene constructs, containing RII beta 5'-flanking sequences and the bacterial CAT structural gene, were transfected into NB2a neuroblastoma cells and ..
  8. Melville Z, Hernández Ochoa E, Pratt S, Liu Y, Pierce A, Wilder P, et al. The Activation of Protein Kinase A by the Calcium-Binding Protein S100A1 Is Independent of Cyclic AMP. Biochemistry. 2017;56:2328-2337 pubmed publisher
  9. Parisiadou L, Yu J, Sgobio C, Xie C, Liu G, Sun L, et al. LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity. Nat Neurosci. 2014;17:367-76 pubmed publisher
    ..Our findings reveal a previously unknown regulatory role for LRRK2 in PKA signaling and suggest a pathogenic mechanism of SPN dysfunction in Parkinson's disease. ..

More Information

Publications45

  1. 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. ..
  2. Inan M, Lu H, Albright M, She W, Crair M. Barrel map development relies on protein kinase A regulatory subunit II beta-mediated cAMP signaling. J Neurosci. 2006;26:4338-49 pubmed
    ..activity mediates barrel map formation using knock-out mice that lack type IIbeta regulatory subunits of PKA (PKARIIbeta)...
  3. Adams M, Brandon E, Chartoff E, Idzerda R, Dorsa D, McKnight G. Loss of haloperidol induced gene expression and catalepsy in protein kinase A-deficient mice. Proc Natl Acad Sci U S A. 1997;94:12157-61 pubmed
    ..These results establish a direct role for protein kinase A as a mediator of haloperidol induced gene induction and cataleptic behavior...
  4. 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...
  5. Pechnick R, Zonis S, Wawrowsky K, Pourmorady J, Chesnokova V. p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus. Proc Natl Acad Sci U S A. 2008;105:1358-63 pubmed publisher
    ..Because many antidepressants stimulate neurogenesis, it is possible that their shared common mechanism of action is suppression of p21. ..
  6. Carlson S, O Buckley T, Thomas R, Thiele T, Morrow A. Altered GABAA receptor expression and seizure threshold following acute ethanol challenge in mice lacking the RII? subunit of PKA. Neurochem Res. 2014;39:1079-87 pubmed publisher
    ..PKA may protect against ethanol-induced deficits in synaptic ?1 and extrasynaptic ?4 receptors, but may facilitate the increase of synaptic ?4 receptors. ..
  7. Ilouz R, Bubis J, Wu J, Yim Y, Deal M, Kornev A, et al. Localization and quaternary structure of the PKA RI? holoenzyme. Proc Natl Acad Sci U S A. 2012;109:12443-8 pubmed publisher
    ..The creation of discrete isoform-specific PKA holoenzyme signaling "foci" paves the way for exploring further biological roles of PKA RI? and establishes a paradigm for PKA signaling. ..
  8. Zhang P, Ye F, Bastidas A, Kornev A, Wu J, Ginsberg M, et al. An Isoform-Specific Myristylation Switch Targets Type II PKA Holoenzymes to Membranes. Structure. 2015;23:1563-1572 pubmed publisher
    ..This membrane-anchoring myristylation switch is independent of A Kinase Anchoring Proteins (AKAPs) that target PKA to membranes by other mechanisms. ..
  9. 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. ..
  10. Watson R, Abdel Majid R, Barnett M, Willis B, Katsnelson A, Gillingwater T, et al. Involvement of protein kinase A in patterning of the mouse somatosensory cortex. J Neurosci. 2006;26:5393-401 pubmed
    ..These results give insight into activity-dependent mechanisms that regulate barrel formation. ..
  11. Ferraro F, Sparta D, Knapp D, Breese G, Thiele T. Increased consumption but not operant self-administration of ethanol in mice lacking the RIIbeta subunit of protein kinase A. Alcohol Clin Exp Res. 2006;30:825-35 pubmed
  12. Zhou T, Li J, Zhao P, Liu H, Jia D, Jia H, et al. Palmitoyl acyltransferase Aph2 in cardiac function and the development of cardiomyopathy. Proc Natl Acad Sci U S A. 2015;112:15666-71 pubmed publisher
    ..These findings establish Aph2 as a critical in vivo regulator of cardiac function and reveal roles for protein palmitoylation in the development of other organs including eyes. ..
  13. Newhall K, Cummings D, Nolan M, McKnight G. Deletion of the RIIbeta-subunit of protein kinase A decreases body weight and increases energy expenditure in the obese, leptin-deficient ob/ob mouse. Mol Endocrinol. 2005;19:982-91 pubmed
    ..These findings indicate that PKA modifies the phenotype of the leptin-deficient mouse, leading to increases in both thermogenesis and energy expenditure. ..
  14. Koh M, Clarke S, Spray K, Thiele T, Bernstein I. Conditioned taste aversion memory and c-Fos induction are disrupted in RIIbeta-protein kinase A mutant mice. Behav Brain Res. 2003;143:57-63 pubmed
    ..These findings suggest that disruption of PKA signaling interferes with LTM consolidation of CTA and that a possible mediator of this effect is interference with c-Fos expression in amygdala which may be necessary for CTA memory. ..
  15. Thiele T, Willis B, Stadler J, Reynolds J, Bernstein I, McKnight G. High ethanol consumption and low sensitivity to ethanol-induced sedation in protein kinase A-mutant mice. J Neurosci. 2000;20:RC75 pubmed
    ..These data demonstrate a role for the RIIbeta subunit of PKA in regulating voluntary consumption of alcohol and sensitivity to the intoxication effects that are produced by this drug. ..
  16. Fischer Q, Beaver C, Yang Y, Rao Y, Jakobsdottir K, Storm D, et al. Requirement for the RIIbeta isoform of PKA, but not calcium-stimulated adenylyl cyclase, in visual cortical plasticity. J Neurosci. 2004;24:9049-58 pubmed
  17. Czyzyk T, Sikorski M, Yang L, McKnight G. Disruption of the RIIbeta subunit of PKA reverses the obesity syndrome of Agouti lethal yellow mice. Proc Natl Acad Sci U S A. 2008;105:276-81 pubmed publisher
    ..These results suggest that the RIIbeta gene mutation alters adiposity and locomotor activity by modifying PKA signaling pathways downstream of the agouti antagonism of MC4R in the hypothalamus. ..
  18. 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 growth...
  19. Enns L, Morton J, Treuting P, Emond M, Wolf N, Dai D, et al. Disruption of protein kinase A in mice enhances healthy aging. PLoS ONE. 2009;4:e5963 pubmed publisher
    ..These findings help establish the highly conserved nature of PKA and suggest that disruption of PKA affects physiological mechanisms known to be associated with healthy aging. ..
  20. Yang L, McKnight G. Hypothalamic PKA regulates leptin sensitivity and adiposity. Nat Commun. 2015;6:8237 pubmed publisher
    ..Our findings suggest that RIIβ-PKA modulates the duration of leptin receptor signalling and therefore the magnitude of the catabolic response to leptin. ..
  21. Tuson M, He M, Anderson K. Protein kinase A acts at the basal body of the primary cilium to prevent Gli2 activation and ventralization of the mouse neural tube. Development. 2011;138:4921-30 pubmed publisher
  22. 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. ..
  23. 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
    ..to an unregulated PKA catalytic subunit and increased PKA type II (PKA-II) activity mediated by the PRKAR2A and PRKAR2B subunits...
  24. Zheng R, Yang L, Sikorski M, Enns L, Czyzyk T, Ladiges W, et al. Deficiency of the RII? subunit of PKA affects locomotor activity and energy homeostasis in distinct neuronal populations. Proc Natl Acad Sci U S A. 2013;110:E1631-40 pubmed publisher
    ..These data demonstrate that RII?-PKA deficiency in a subset of hypothalamic GABAergic neurons leads to the lean phenotype. ..
  25. Luo Z, Singh I, 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. J Biol Chem. 1992;267:24738-47 pubmed
    The 5'-flanking DNA of the mouse RII beta subunit of the cAMP-dependent protein kinase gene was characterized by transient transfection of RII beta-CAT constructs into mouse neuroblastoma cells (NB2a) and Chinese hamster ovary (CHO) ..
  26. Su J, Wu W, Huang S, Xue R, Wang Y, Wan Y, et al. PKA-RIIB Deficiency Induces Brown Fatlike Adipocytes in Inguinal WAT and Promotes Energy Expenditure in Male FVB/NJ Mice. Endocrinology. 2017;158:578-591 pubmed publisher
    ..PKA-RIIB, encoded by the Prkar2b gene, is most abundant in BAT and white adipose tissue (WAT) and in the brain...
  27. 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 RIIα and RIIβ, respectively) are also viable but have not been studied for their ..
  28. Star E, Zhu M, Shi Z, Liu H, Pashmforoush M, Sauve Y, et al. Regulation of retinal interneuron subtype identity by the Iroquois homeobox gene Irx6. Development. 2012;139:4644-55 pubmed publisher
    ..This work provides insight into the generation of neuronal subtypes by revealing a mechanism in which opposing, yet interdependent, transcription factors regulate subtype identity. ..
  29. Zhang P, Smith Nguyen E, Keshwani M, Deal M, Kornev A, Taylor S. Structure and allostery of the PKA RII? tetrameric holoenzyme. Science. 2012;335:712-6 pubmed publisher
    ..The quaternary structure of the RII? tetramer differs appreciably from our model of the RI? tetramer, confirming the small-angle x-ray scattering prediction that the structures of each PKA tetramer are different. ..
  30. 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
  31. Brandon E, Logue S, Adams M, Qi M, Sullivan S, Matsumoto A, et al. Defective motor behavior and neural gene expression in RIIbeta-protein kinase A mutant mice. J Neurosci. 1998;18:3639-49 pubmed
    ..These results demonstrate that motor learning and the regulation of neuronal gene expression require RIIbeta PKA, whereas the acute locomotor effects of dopaminergic drugs are relatively unaffected by this PKA deficiency. ..
  32. Brandon E, Gerhold K, Qi M, McKnight G, Idzerda R. Derivation of novel embryonic stem cell lines and targeting of cyclic AMP-dependent protein kinase genes. Recent Prog Horm Res. 1995;50:403-8 pubmed
  33. Zhang P, Knape M, Ahuja L, Keshwani M, King C, Sastri M, et al. Single Turnover Autophosphorylation Cycle of the PKA RIIβ Holoenzyme. PLoS Biol. 2015;13:e1002192 pubmed publisher
    ..This previously unappreciated molecular mechanism is an integral part of PKA signaling for type II holoenzymes. ..
  34. Jain A, Liu R, Ramani B, Arauz E, Ishitsuka Y, Ragunathan K, et al. Probing cellular protein complexes using single-molecule pull-down. Nature. 2011;473:484-8 pubmed publisher
    ..SiMPull should provide a rapid, sensitive and robust platform for analysing protein assemblies in biological pathways. ..
  35. Nagalla S, Shaw C, Kong X, Kondkar A, Edelstein L, Ma L, et al. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood. 2011;117:5189-97 pubmed publisher
    ..Three miRNA-mRNA pairs (miR-200b:PRKAR2B, miR-495:KLHL5, and miR-107:CLOCK) were selected from this list, and all 3 miRNAs knocked down protein expression ..
  36. Fee J, Knapp D, Sparta D, Breese G, Picker M, Thiele T. Involvement of protein kinase A in ethanol-induced locomotor activity and sensitization. Neuroscience. 2006;140:21-31 pubmed