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Gene Review

Prkaca  -  protein kinase, cAMP dependent, catalytic,...

Mus musculus

Synonyms: C alpha, Cs, PKA, PKA C-alpha, PKCD, ...
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Disease relevance of Prkaca


Psychiatry related information on Prkaca

  • PKA phosphorylations of tau may be an early event in the development of neurofibrillary pathology in Alzheimer's disease [6].
  • Polymerase chain reaction experiments demonstrate that the two functional variable gene segments (V delta and V alpha/delta) are expressed individually with both C alpha and C delta genes as mRNA, indicating a permissiveness in their expression patterns [7].
  • We report that mice with the targeted disruption of one Gsalpha allele as well as mice with reduced neuronal PKA activity have decreased alcohol consumption compared with their wild-type littermates [8].
  • The tail withdrawal and the hot plate reaction time expressed as percent maximum possible effect (%MPE) was increased to 80-100 and 41-90%, respectively, in PKC and PKA inhibitor-treated morphine tolerant mice compared to 2-10% in non-treated mice [9].

High impact information on Prkaca

  • The beneficial effect of the Uch-L1 fusion protein is associated with restoration of normal levels of the PKA-regulatory subunit IIalpha, PKA activity, and CREB phosphorylation [10].
  • We show here that the minimal alpha enhancer is active in the gamma delta T cell lineage but gains alpha beta lineage specificity through negative cis-acting elements 3' of the C alpha gene that silence the enhancer in gamma delta T cells [11].
  • We have constructed a hybrid immunoglobulin (VDJH)-T cell receptor (C alpha) gene using the VDJH exon from a digoxin-specific antibody [12].
  • We have found that the myc oncogene has been modified by abortive recombination with the alpha heavy-chain immunoglobulin constant-region (C alpha) gene in five different mouse plasmacytoma lines [13].
  • To probe mechanisms operating at the CH gene locus during normal B lymphocyte differentiation, we have used cloned probes for the constant region genes Cmu, C gamma 1 and C alpha to analyze the immunoglobulin heavy chain genes of three kinds of cell populations in successive stages of B cell development [14].

Chemical compound and disease context of Prkaca

  • Treatment of glioblastoma U-87 by systemic administration of an antisense protein kinase C-alpha phosphorothioate oligodeoxynucleotide [15].
  • PKA-dependent growth stimulation of cells derived from human pulmonary adenocarcinoma and small airway epithelium by dexamethasone [16].
  • Our laboratory has found that Chinese hamster ovary (CHO) and mouse Y1 adrenocortical carcinoma PKA mutants with a defective R subunit, but not altered C subunits, exhibit increased resistance to cisplatin as well as other DNA-damaging agents [17].
  • However, the treatment of LPS-stimulated 38B9 cells with pertussis toxin (PTX), an inhibitor for the G protein-coupled receptor, inhibited the activation of both PKC- and PKA-dependent ERK and significantly reduced LPS-induced proliferation but not IgG secretion [18].
  • Kinase-negative mutants of S49 mouse lymphoma cells, which lack detectable catalytic (C) subunit of cyclic AMP-dependent protein kinase, nevertheless contain cytoplasmic mRNAs for the two major forms of C subunit, C alpha and C beta [19].

Biological context of Prkaca


Anatomical context of Prkaca


Associations of Prkaca with chemical compounds

  • Signaling through cyclic AMP to activate PKA was found to inhibit envelope-induced cell-cell fusion, whereas treatment of cells with PKA inhibitors H89, KT5720, and PKA Catalpha siRNA all enhanced this cell fusion process [28].
  • These data show that the insulin-stimulated oxidant signal differentially affects the two major downstream components of the insulin signaling pathway, PI 3'-kinase and MAP kinase, and cross-talk between insulin action, PLCgamma and, to a lesser extent, PKA modulates the net cellular effects of insulin-stimulated cellular H(2)O(2) [29].
  • In vitro phosphorylation of recombinant mouse LASP-1 by cAMP- and cGMP-dependent protein kinase (PKA and PKG, respectively) occurs at serine 61, serine 99, and threonine 156 whereas in intact cells mouse LASP-1 is phosphorylated only at threonine 156 [30].
  • This is displaced from its functional homologs, C alpha and C beta, which we map to mouse Chrs 8 (band C3) and 3 (band H3), respectively [31].
  • Separate activation of the cAMP/PKA pathway by 8-Br-cAMP was completely prevented by PD098059 whereas activation of the PLC/PKC pathway by the PKC activator 1,2-dioctanoyl-sn-glycerol (DOG) and the PKG pathway by 8-Br-cGMP induced internalization of NaPi-IIa which could be only partly blocked by PD 098059 [32].

Physical interactions of Prkaca


Enzymatic interactions of Prkaca

  • In the parental S194 cells, one allele of the c-myc was rearranged and its 5'-flanking region was partially deleted by recombination with the immunoglobulin C alpha gene [35].

Regulatory relationships of Prkaca

  • Experimental data indicate that exogenous IFN-gamma stimulated cAMP accumulation and PKA activation in time-dependent and dose-dependent manners in murine peritoneal macrophages [36].
  • Also, signaling pathways downstream of PKA and PKC induce the expression of Foxc2 mRNA [37].
  • Modeling the VPAC2-activated cAMP/PKA signaling pathway: from receptor to circadian clock gene induction [38].
  • We report that kinase suppressor of Ras (KSR1) functions biochemically in the hippocampus to scaffold the components of the ERK cascade, specifically regulating the cascade when a membrane fraction of ERK is activated via a PKC-dependent pathway but not via a cAMP/PKA-dependent pathway [39].
  • Perturbation of the expression of the catalytic subunit C alpha of cyclic AMP-dependent protein kinase inhibits TCR-triggered secretion of IL-2 by T helper hybridoma cells [40].

Other interactions of Prkaca


Analytical, diagnostic and therapeutic context of Prkaca


  1. MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype. Ways, D.K., Kukoly, C.A., deVente, J., Hooker, J.L., Bryant, W.O., Posekany, K.J., Fletcher, D.J., Cook, P.P., Parker, P.J. J. Clin. Invest. (1995) [Pubmed]
  2. 12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated hydrolysis of inositol phospholipids. Liu, B., Khan, W.A., Hannun, Y.A., Timar, J., Taylor, J.D., Lundy, S., Butovich, I., Honn, K.V. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Increased protein kinase C alpha expression in human colonic Caco-2 cells after insertion of human Ha-ras or polyoma virus middle T oncogenes. Delage, S., Chastre, E., Empereur, S., Wicek, D., Veissiére, D., Capeau, J., Gespach, C., Cherqui, G. Cancer Res. (1993) [Pubmed]
  4. Diminished loss of proteoglycans and lack of albuminuria in protein kinase C-alpha-deficient diabetic mice. Menne, J., Park, J.K., Boehne, M., Elger, M., Lindschau, C., Kirsch, T., Meier, M., Gueler, F., Fiebeler, A., Bahlmann, F.H., Leitges, M., Haller, H. Diabetes (2004) [Pubmed]
  5. Activation-induced depletion of protein kinase C alpha provokes desensitization of monocytes/macrophages in sepsis. von Knethen, A., Tautenhahn, A., Link, H., Lindemann, D., Brüne, B. J. Immunol. (2005) [Pubmed]
  6. PKA phosphorylations on tau: developmental studies in the mouse. Andorfer, C.A., Davies, P. Dev. Neurosci. (2000) [Pubmed]
  7. Organization, sequence, and function of 34.5 kb of genomic DNA encompassing several murine T-cell receptor alpha/delta variable gene segments. Seto, D., Koop, B.F., Deshpande, P., Howard, S., Seto, J., Wilk, E., Wang, K., Hood, L. Genomics (1994) [Pubmed]
  8. The cAMP-protein kinase A signal transduction pathway modulates ethanol consumption and sedative effects of ethanol. Wand, G., Levine, M., Zweifel, L., Schwindinger, W., Abel, T. J. Neurosci. (2001) [Pubmed]
  9. PKC and PKA inhibitors reinstate morphine-induced behaviors in morphine tolerant mice. Smith, F.L., Javed, R.R., Smith, P.A., Dewey, W.L., Gabra, B.H. Pharmacol. Res. (2006) [Pubmed]
  10. Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Gong, B., Cao, Z., Zheng, P., Vitolo, O.V., Liu, S., Staniszewski, A., Moolman, D., Zhang, H., Shelanski, M., Arancio, O. Cell (2006) [Pubmed]
  11. Alpha beta lineage-specific expression of the alpha T cell receptor gene by nearby silencers. Winoto, A., Baltimore, D. Cell (1989) [Pubmed]
  12. Expression of a hybrid immunoglobulin-T cell receptor protein in transgenic mice. Becker, M.L., Near, R., Mudgett-Hunter, M., Margolies, M.N., Kubo, R.T., Kaye, J., Hedrick, S.M. Cell (1989) [Pubmed]
  13. Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Shen-Ong, G.L., Keath, E.J., Piccoli, S.P., Cole, M.D. Cell (1982) [Pubmed]
  14. CH gene rearrangements in IgM-bearing B cells and in the normal splenic DNA component of hybridomas making different isotypes of antibody. Hurwitz, J.L., Coleclough, C., Cebra, J.J. Cell (1980) [Pubmed]
  15. Treatment of glioblastoma U-87 by systemic administration of an antisense protein kinase C-alpha phosphorothioate oligodeoxynucleotide. Yazaki, T., Ahmad, S., Chahlavi, A., Zylber-Katz, E., Dean, N.M., Rabkin, S.D., Martuza, R.L., Glazer, R.I. Mol. Pharmacol. (1996) [Pubmed]
  16. PKA-dependent growth stimulation of cells derived from human pulmonary adenocarcinoma and small airway epithelium by dexamethasone. Al-Wadei, H.A., Takahasi, T., Schuller, H.M. Eur. J. Cancer (2005) [Pubmed]
  17. Effects of RIalpha overexpression on cisplatin sensitivity in human ovarian carcinoma cells. Cvijic, M.E., Chin, K.V. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  18. A G protein-associated ERK pathway is involved in LPS-induced proliferation and a PTK-associated p38 MAPK pathway is involved in LPS-induced differentiation in resting B cells. Kim, J., Yang, H.Y., Jang, Y.S. Mol. Immunol. (2006) [Pubmed]
  19. A kinase-negative mutant of S49 mouse lymphoma cells is defective in posttranslational maturation of catalytic subunit of cyclic AMP-dependent protein kinase. Steinberg, R.A. Mol. Cell. Biol. (1991) [Pubmed]
  20. 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. Imaizumi-Scherrer, T., Faust, D.M., Bénichou, J.C., Hellio, R., Weiss, M.C. J. Cell Biol. (1996) [Pubmed]
  21. A mitogenic signal triggered at an early stage of vaccinia virus infection: implication of MEK/ERK and protein kinase A in virus multiplication. de Magalhães, J.C., Andrade, A.A., Silva, P.N., Sousa, L.P., Ropert, C., Ferreira, P.C., Kroon, E.G., Gazzinelli, R.T., Bonjardim, C.A. J. Biol. Chem. (2001) [Pubmed]
  22. Characterization of genomic clones coding for the C alpha and C beta subunits of mouse cAMP-dependent protein kinase. Chrivia, J.C., Uhler, M.D., McKnight, G.S. J. Biol. Chem. (1988) [Pubmed]
  23. Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway. Schulte, T.W., Blagosklonny, M.V., Romanova, L., Mushinski, J.F., Monia, B.P., Johnston, J.F., Nguyen, P., Trepel, J., Neckers, L.M. Mol. Cell. Biol. (1996) [Pubmed]
  24. Regulation of lipoprotein lipase by protein kinase C alpha in 3T3-F442A adipocytes. Ranganathan, G., Song, W., Dean, N., Monia, B., Barger, S.W., Kern, P.A. J. Biol. Chem. (2002) [Pubmed]
  25. A novel protein kinase C alpha-dependent signal to ERK1/2 activated by alphaVbeta3 integrin in osteoclasts and in Chinese hamster ovary (CHO) cells. Rucci, N., DiGiacinto, C., Orrù, L., Millimaggi, D., Baron, R., Teti, A. J. Cell. Sci. (2005) [Pubmed]
  26. 1-(5-oxohexyl)-3,7-Dimethylxanthine, a phosphodiesterase inhibitor, activates MAPK cascades and promotes osteoblast differentiation by a mechanism independent of PKA activation (pentoxifylline promotes osteoblast differentiation). Rawadi, G., Ferrer, C., Spinella-Jaegle, S., Roman-Roman, S., Bouali, Y., Baron, R. Endocrinology (2001) [Pubmed]
  27. Participation of protein kinase C alpha isoform and extracellular signal-regulated kinase in neurite outgrowth of GT1 hypothalamic neurons. Choe, Y., Lee, B.J., Kim, K. J. Neurochem. (2002) [Pubmed]
  28. Cell signaling through the protein kinases cAMP-dependent protein kinase, protein kinase Cepsilon, and RAF-1 regulates amphotropic murine leukemia virus envelope protein-induced syncytium formation. Wang, W., Jobbagy, Z., Bird, T.H., Eiden, M.V., Anderson, W.B. J. Biol. Chem. (2005) [Pubmed]
  29. Integration of multiple downstream signals determines the net effect of insulin on MAP kinase vs. PI 3'-kinase activation: potential role of insulin-stimulated H(2)O(2). Mahadev, K., Wu, X., Motoshima, H., Goldstein, B.J. Cell. Signal. (2004) [Pubmed]
  30. Phosphorylation of mouse LASP-1 on threonine 156 by cAMP- and cGMP-dependent protein kinase. Keicher, C., Gambaryan, S., Schulze, E., Marcus, K., Meyer, H.E., Butt, E. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  31. Cloning of a mouse protein kinase A catalytic subunit pseudogene and chromosomal mapping of C subunit isoforms. Cummings, D.E., Edelhoff, S., Disteche, C.M., McKnight, G.S. Mamm. Genome (1994) [Pubmed]
  32. Involvement of the MAPK-kinase pathway in the PTH-mediated regulation of the proximal tubule type IIa Na+/Pi cotransporter in mouse kidney. Bacic, D., Schulz, N., Biber, J., Kaissling, B., Murer, H., Wagner, C.A. Pflugers Arch. (2003) [Pubmed]
  33. Phosphorylation of transglutaminase 2 by PKA at Ser216 creates 14-3-3 binding sites. Mishra, S., Murphy, L.J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  34. Comparative analysis of human and mouse 3' Igh regulatory regions identifies distinctive structural features. Sepulveda, M.A., Garrett, F.E., Price-Whelan, A., Birshtein, B.K. Mol. Immunol. (2005) [Pubmed]
  35. c-myc expression and transformed phenotypes in hybrid clones between mouse plasmacytoma S194 cells and normal spleen cells or fibroblasts. Oikawa, T., Yuhki, Y., Kondoh, N., Abe, K., Yuhki, N., Ogiso, Y., Kuzumaki, N. Int. J. Cancer (1988) [Pubmed]
  36. IFN-gamma activates cAMP/PKA/CREB signaling pathway in murine peritoneal macrophages. Liu, L., Wang, Y., Fan, Y., Li, C.L., Chang, Z.L. J. Interferon Cytokine Res. (2004) [Pubmed]
  37. Insulin and TNF alpha induce expression of the forkhead transcription factor gene Foxc2 in 3T3-L1 adipocytes via PI3K and ERK 1/2-dependent pathways. Grønning, L.M., Cederberg, A., Miura, N., Enerbäck, S., Taskén, K. Mol. Endocrinol. (2002) [Pubmed]
  38. Modeling the VPAC2-activated cAMP/PKA signaling pathway: from receptor to circadian clock gene induction. Hao, H., Zak, D.E., Sauter, T., Schwaber, J., Ogunnaike, B.A. Biophys. J. (2006) [Pubmed]
  39. Kinase suppressor of Ras1 compartmentalizes hippocampal signal transduction and subserves synaptic plasticity and memory formation. Shalin, S.C., Hernandez, C.M., Dougherty, M.K., Morrison, D.K., Sweatt, J.D. Neuron (2006) [Pubmed]
  40. Perturbation of the expression of the catalytic subunit C alpha of cyclic AMP-dependent protein kinase inhibits TCR-triggered secretion of IL-2 by T helper hybridoma cells. Sugiyama, H., Chen, P., Hunter, M.G., Sitkovsky, M.V. J. Immunol. (1997) [Pubmed]
  41. Phosphorylation of nuclear phospholipase C beta1 by extracellular signal-regulated kinase mediates the mitogenic action of insulin-like growth factor I. Xu, A., Suh, P.G., Marmy-Conus, N., Pearson, R.B., Seok, O.Y., Cocco, L., Gilmour, R.S. Mol. Cell. Biol. (2001) [Pubmed]
  42. Cell type-specific upregulation of myristoylated alanine-rich C kinase substrate and protein kinase C-alpha, -beta I, -beta II, and -delta in microglia following kainic acid-induced seizures. Eun, S.Y., Kim, E.H., Kang, K.S., Kim, H.J., Jo, S.A., Kim, S.J., Jo, S.H., Kim, S.J., Blackshear, P.J., Kim, J. Exp. Mol. Med. (2006) [Pubmed]
  43. Regulation of interleukin-10 secretion by histamine in TH2 cells and splenocytes. Osna, N., Elliott, K., Khan, M.M. Int. Immunopharmacol. (2001) [Pubmed]
  44. Evidence for a second isoform of the catalytic subunit of cAMP-dependent protein kinase. Uhler, M.D., Chrivia, J.C., McKnight, G.S. J. Biol. Chem. (1986) [Pubmed]
  45. Protein kinase A translocation and insulin secretion in pancreatic beta-cells: studies with adenylate cyclase toxin from Bordetella pertussis. Gao, Z., Young, R.A., Trucco, M.M., Greene, S.R., Hewlett, E.L., Matschinsky, F.M., Wolf, B.A. Biochem. J. (2002) [Pubmed]
  46. Molecular cloning of a tissue-specific protein kinase (C gamma) from human testis--representing a third isoform for the catalytic subunit of cAMP-dependent protein kinase. Beebe, S.J., Oyen, O., Sandberg, M., Frøysa, A., Hansson, V., Jahnsen, T. Mol. Endocrinol. (1990) [Pubmed]
  47. Intraplantar PGE(2) causes nociceptive behaviour and mechanical allodynia: the role of prostanoid E receptors and protein kinases. Kassuya, C.A., Ferreira, J., Claudino, R.F., Calixto, J.B. Br. J. Pharmacol. (2007) [Pubmed]
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