Disease relevance of Prkaca

• 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 [1].
• 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 [2].
• Increased protein kinase C alpha expression in human colonic Caco-2 cells after insertion of human Ha-ras or polyoma virus middle T oncogenes [3].
• Diminished loss of proteoglycans and lack of albuminuria in protein kinase C-alpha-deficient diabetic mice [4].
• Activation-induced depletion of protein kinase C alpha provokes desensitization of monocytes/macrophages in sepsis [5].

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

• PKA could be implicated in the establishment and/or maintenance of the unique pattern of gene expression occurring at the junction, or in the modulation of synaptic activity via protein phosphorylation [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 [20].
• Embryonic skeletal muscle shows a high level of C alpha transcripts and protein throughout the fiber; the transcripts are already present by day 12 of embryogenesis, and their elevated level is maintained only through fetal life [20].
• Taken together, our data provide evidence that the early mitogenic signal triggered upon VV infection relies upon the activation of the protein kinases MEK, ERK, and PKA, which are needed for both signal transduction and virus multiplication [21].
• The C alpha gene is divided into 10 exons contained on three overlapping clones [22].

Anatomical context of Prkaca

• Using the model system of NIH 3T3 cells stimulated with phorbol 12-myristate 13-acetate (PMA), we show that GA does not affect the ability of protein kinase C alpha to be activated by phorbol esters, but it does block activation of MEK and MAPK [23].
• Regulation of lipoprotein lipase by protein kinase C alpha in 3T3-F442A adipocytes [24].
• A novel protein kinase C alpha-dependent signal to ERK1/2 activated by alphaVbeta3 integrin in osteoclasts and in Chinese hamster ovary (CHO) cells [25].
• 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) [26].
• Participation of protein kinase C alpha isoform and extracellular signal-regulated kinase in neurite outgrowth of GT1 hypothalamic neurons [27].

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

• In summary, we provide convincing evidence that phosphorylation of TG2 by PKA creates binding site(s) for 14-3-3 both in vitro and in vivo [33].
• Immunoglobulin heavy chain (Igh) locus rearrangements are controlled in part by an approximately 30 b complex 3' regulatory region located 3' of C alpha: this region contains several enhancers [34].

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

• In addition, RI alpha recruits C alpha protein to the junction, providing at this site the potential for local responsiveness to cAMP [20].
• In vitro studies revealed that recombinant PLC beta1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by PKA [41].
• IFN-gamma activates cAMP/PKA/CREB signaling pathway in murine peritoneal macrophages [36].
• 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 [42].
• This study was designed to assess the role of histamine in the regulation of IL-10 production and the involvement of PKA and STAT factors in this process [43].

Analytical, diagnostic and therapeutic context of Prkaca

• C alpha cDNA clones hybridize to a 2.4-kilobase mRNA on Northern blots whereas C beta cDNA clones detect a 4.3-kilobase mRNA [44].
• Genomic clones containing the 5' end of the C beta gene were also isolated, and sequence analysis demonstrated that the positions of the three introns examined are identical in the C alpha and C beta genes [22].
• PKA alpha, beta and gamma catalytic subunits (Calpha, Cbeta and Cgamma respectively) were identified in betaTC6 cells by confocal microscopy [45].
• In the present study, we report the molecular cloning of a third isoform of C, from a human testis cDNA library, as well as the isolation of human cDNAs for C alpha and C beta [46].
• Western blot analyses confirmed that i.pl. injection of PGE(2) activated PKA, PKCalpha, and mitogen activated kinases (MAPKs) in the paw [47].

References