Disease relevance of Prkcb1

• PKCbeta regulates ischemia/reperfusion injury in the lung [1].
• Diabetic PKC-beta(-/-) mice were protected from renal hypertrophy, glomerular enlargement, and hyperfiltration observed in diabetic wild-type mice and had less proteinuria [2].
• Whereas wild-type mice exposed to hypoxia (6%) displayed a robust increase in tissue factor transcripts and antigen, and vascular fibrin deposition, PKCbeta null animals showed a markedly blunted response [3].
• We tested this hypothesis by inducing diabetic nephropathy in PKC-beta-deficient (PKC-beta(-/-)) mice [4].
• Inhibition of PKC-beta promoted cell death in B lymphomas characterized by exaggerated NF-kappa B activity [5].

Psychiatry related information on Prkcb1

• Previously, it had been demonstrated that PKC beta II immunoreactivity is decreased in the caudate-putamen of patients with Huntington's disease [6].

High impact information on Prkcb1

• Only PKC beta mRNA was detected in normal murine T lymphocytes [7].
• The mutant T lymphocytes contained amounts of 4.4 kb PKC beta message similar to those in normal murine lymphocytes, but the 2.9 kb and 1.2 kb messages found in normal lymphocytes were barely detectable [7].
• Here, we demonstrate that PKC-beta is specifically required for B cell receptor (BCR)-mediated NF-kappa B activation [5].
• IKK is also recruited to the CARMA1-Bcl10-mucosal-associated lymphoid tissue 1 adaptor complex in a PKCbeta-dependent manner [8].
• Expression of the immediate early gene, early growth response-1 (Egr-1), and its downstream target genes was significantly increased in WT mice in I/R, particularly in mononuclear phagocytes (MPs), whereas this expression was attenuated in PKCbeta-null mice or WT mice fed ruboxistaurin [1].

Chemical compound and disease context of Prkcb1

• To determine whether the decreased level of PKC-beta 2 within LCs was associated with an alteration in contact hypersensitivity, we treated mice with only a single application of TPA, and 6 hours later mice were sensitized with 2,4-dinitrofluorobenzene on the same dorsal area [9].
• Palmitoylcarnitine, reported previously to promote neuronal differentiation, was observed to affect distribution of protein kinase C (PKC) isoforms in neuroblastoma NB-2a cells, leading to retardation in cytoplasm of high molecular weight species of PKCbeta and delta [10].

Biological context of Prkcb1

• The inhibition of exocytosis in the PKCbeta-deficient mast cells occurred whether the stimuli were due to the aggregation of the mast cell surface FcepsilonRI or to the calcium ionophore, ionomycin [11].
• Increases in urinary isoprostane and 8-hydroxydeoxyguanosine, parameters of oxidative stress, in diabetic PKC-beta(-/-) mice were significantly reduced compared with diabetic wild-type mice [2].
• These rapid increases in nuclear DAG and PKC beta II expression suggest a mechanism for EPO-induced changes in gene expression necessary for cell proliferation [12].
• To establish whether PKC activation is sufficient to induce an abnormal phenotype, PKCbeta was conditionally expressed in cardiomyocytes of transgenic mice [13].
• We identified a highly conserved PKCbeta serine phosphorylation site in a short linker within the Tec homology domain of Btk [14].

Anatomical context of Prkcb1

• The loss of the basement membrane proteoglycan perlecan and the podocyte protein nephrin in the diabetic state was not prevented in the PKC-beta(-/-) mice as previously demonstrated in the nonalbuminuric diabetic PKC-alpha(-/-) mice [4].
• F9 stem cells express PKC beta, delta, epsilon, and zeta [15].
• RA-induced differentiation to primitive endoderm led to a transition from PKC beta to PKC alpha expression [15].
• PKC beta was equally distributed in the cytosol and membrane [16].
• Human lymphoid cell lines express large amounts of PKC beta mRNAs in addition to PKC alpha [17].

Associations of Prkcb1 with chemical compounds

• We studied nondiabetic and streptozotocin-induced diabetic PKC-beta(-/-) mice compared with appropriate 129/SV wild-type mice [4].
• When the cells were treated with retinoic acid either alone or in the presence of cAMP for 120 h, PKC alpha mRNA and protein levels increased, whereas those of PKC beta and PKC gamma became undetectable [18].
• PKC transfectants (PKC-beta II, -delta, and -eta) showed substantial protection from cell death induced by the exposure to NO donors such as SNP and S-nitrosoglutathione (GSNO) [19].
• Blocking PKC beta translocation with hispidin resulted in more rapid uptake of wild-type bacteria and greatly reduced escape from the primary phagocytic vacuoles of J774 cells [20].
• Treatment with the calcium channel blocker SK&F 96365 inhibited translocation of PKC beta II but not PKC delta [20].

Regulatory relationships of Prkcb1

• By contrast, PKCbeta is not required for Ser-473 phosphorylation in mast cells stimulated with stem cell factor or interleukin-3, in serum-stimulated fibroblasts, or in antigen receptor-stimulated T or B lymphocytes [21].
• Considering that PKC-beta I and -beta II are coexpressed with PKC-alpha in mouse medullary collecting duct, the present results indicate that conventional PKC isoenzymes cannot fully compensate for each other [22].
• In addition to its role in B cell activation and humoral immunity, PKCbeta was recently shown to control NF-kappaB activation and survival of mature B cells [23].
• The PKCbeta isoform appears to not be involved in the signaling cascades regulating Purkinje cell dendritic maturation in cerebellar slice cultures [24].
• These results suggest that ceramide directly activates PKC beta and promotes calpain-mediated proteolysis in murine PMNs [25].

Other interactions of Prkcb1

• Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCbeta II correlates with intensified fear-induced conflict behavior [26].
• In this study, we found that mast cells derived from PKCbeta-deficient mice produce less interleukin 6 in response to IgE-Ag [11].
• In wild-type mice, diabetes increased the translocation of PKC-alpha and -beta1 to the membrane, whereas only PKC-alpha was elevated in PKC-beta(-/-) mice [2].
• After 8 weeks of diabetes, the high-glucose-induced renal and glomerular hypertrophy, as well as the increased expression of extracellular matrix proteins such as collagen and fibronectin, was reduced in PKC-beta(-/-) mice [4].
• Furthermore, the high-glucose-induced expression of the profibrotic cytokine transforming growth factor (TGF)-beta1 and connective tissue growth factor were significantly diminished in the diabetic PKC-beta(-/-) mice compared with diabetic wild-type mice, suggesting a role of the PKC-beta isoform in the regulation of renal hypertrophy [4].

Analytical, diagnostic and therapeutic context of Prkcb1

• Consistent with a central role for Egr-1 in hypoxia-induced expression of tissue factor, PKCbeta null mice subjected to oxygen deprivation displayed at most a minor elevation in Egr-1 transcripts, antigen, and intensity of the gel shift band by electrophoretic mobility shift assay, compared with normoxic animals [3].
• Using Western blot analysis, PKC beta was found to be the most abundant isoform in monocytes [16].
• Immunoblotting analyses of PKC isozyme protein levels after TPA treatment followed the changes in activity for cytosolic PKC alpha, PKC beta and PKC gamma [27].
• IFN-alpha-induced signaling and gene activation were inhibited by ligation of Fc receptors and Toll-like receptors 7 and 8 in a PKCbeta-dependent manner [28].
• Furthermore, with orthotopical transplantation, PKC-beta inhibition suppressed HCC tumor development in the liver [29].

References