Disease relevance of PRKCG

• The entire coding region of PRKCG was sequenced in an affected member of family AT08 and in a group of 39 unrelated patients with ataxia not attributable to trinucleotide expansions [1].
• Different PRKCG mutations were found in another family with SCA and in a sporadic case from the United States. Axial myoclonus was not observed in any of these US families [2].
• After identifying a PRKCG mutation, DNA samples from 72 patients with multiple system atrophy and 50 healthy individuals were examined for the mutation as controls [2].
• OBJECTIVE: To report a Dutch family with autosomal dominant cerebellar ataxia (ADCA) based on a novel mutation in the PRKCG gene [3].
• PKC-gamma was present in most of the glioblastomas [4].

Psychiatry related information on PRKCG

• Characterization and differential distribution of the three major human protein kinase C isozymes (PKC alpha, PKC beta, and PKC gamma) of the central nervous system in normal and Alzheimer's disease brains [5].

High impact information on PRKCG

• A candidate gene for human neurodegenerative disorders: a rat PKC gamma mutation causes a Parkinsonian syndrome [6].
• Both types of cells, however, expressed the PKC alpha and PKC gamma isoforms [7].
• A particularly compelling candidate gene, PRKCG, encodes protein kinase C gamma (PKC gamma), a member of a family of serine/threonine kinases [1].
• Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia [1].
• These results strongly support a new mechanism for neuronal cell dysfunction and death in hereditary ataxias and suggest that there may be a common pathway for PKC gamma-related and polyglutamine-related neurodegeneration [1].

Chemical compound and disease context of PRKCG

• Mutation of the highly conserved cysteine residue 131 of the SCA14 associated PRKCG gene in a family with slow progressive cerebellar ataxia [8].

Biological context of PRKCG

• No mutations in the coding region of the PRKCG gene in three families with retinitis pigmentosa linked to the RP11 locus on chromosome 19q [9].
• CONCLUSION: A SCA-14-linked Dutch ADCA family with a novel missense mutation in the PRKCG gene was identified [3].
• Exons 4 and 5 of the candidate gene, PRKCG, were sequenced [3].
• All six SCA14 families were French and there was no evidence of reduced penetrance [10].
• Point mutations in the gene encoding protein kinase Cgamma (PRKCG) are responsible for spinocerebellar ataxia 14 (SCA14) [10].

Anatomical context of PRKCG

• PKC-gamma was also down-regulated in the presence of PMA, but there was no evidence for translocation to the plasma membrane or nuclear fraction [4].
• Earlier studies identified PKC-alpha and PKC-gamma in these cell lines but PKC-beta was not present [11].
• All lymphoid leukemic cells expressed PKC-gamma in the cytosol fractions, albeit a minor component; however, this type was observed in cells from only half the number of AML patients [12].
• Constitutive expression of PKC beta and PKC gamma isoforms was low in HeLa cells and was not affected significantly by TPA or lyngbyatoxin A analogues.(ABSTRACT TRUNCATED AT 250 WORDS)[13]
• No PKC gamma was detected in T lymphocytes [14].

Associations of PRKCG with chemical compounds

• Immunoblots with isoenzyme-specific anti-PKC monoclonal antibodies demonstrated expression of immunoreactive PKC alpha, PKC beta and PKC gamma proteins that were translocated to the membrane upon TPA plus ionomycin stimulation [15].
• Based on the recent description of three missense mutations in the PRKCG gene, located within the boundaries of the SCA-14 locus, we sequenced exons 4 and 5 of this gene and detected a novel missense mutation in exon 4, which involves a G-->A transition in nucleotide 353 and results in a glycine-to-aspartic acid substitution at residue 118 [3].
• We describe a novel mutation in exon 5 of the PRKCG gene, altering a highly conserved cysteine to a phenylalanine at codon 150, and record the detailed clinical observations in six affected family members [16].
• The G/T missense mutation occurred in exon 2 of PRKCG and results in a substitution of glycine by valine (G63V) in the evolutionarily highly conserved cysteine-rich region 1/C1 domain of PRKCG [17].
• The PRKCG gene encodes the protein kinase Cgamma (PKCgamma), a member of a serine/threonine kinase family involved in signal transduction important for several cellular processes, including cell proliferation and synaptic transmission [18].

Physical interactions of PRKCG

• Our results suggest that PKC gamma binds directly to GluR4, thereby modulating the function of GluR4-containing AMPA receptors [19].

Regulatory relationships of PRKCG

• Additionally, PKC gamma and to a lesser extent PKC lambda isoforms were induced in reactive astrocytes in proximity to amyloid plaques [20].
• Thus, integrin-dependent adhesion of HSG cells to fibronectin or collagen I activated PKC-gamma and PKC-delta [21].
• Cell clones obtained by the transfection of PKC gamma cDNA express 3.6 to 5 times more PKC activity than parental cells that express predominantly endogenous PKC alpha [22].

Other interactions of PRKCG

• When levels of the four isoforms in the tumor cells were compared to levels in the normal cells, no increase was observed in PKC-alpha or PKC-gamma, but PKC-epsilon was elevated three to 30 times in six of the eight tumors, and PKC-zeta was elevated approximately two times in all of the tumors [11].
• Presence of RARbeta correlated significantly (and positively) with the expression of PKC-gamma and -zeta and also in relation to the infection and recurrence status [23].
• We first determined the genomic structure of the PSCD2 and PRKCG genes, and performed mutation analysis of all exons and exon-intron junctions of the four genes, in the PJS07 family [24].
• We screened for mutations in the PRKCG gene, in a large series of 284 ADCA index cases, mostly French (n=204) and German (n=48), in whom CAG repeat expansions in the known SCA genes were previously excluded [10].
• Additionally, PKC gamma expression in GluR4 transfected human embryonic kidney 293T cells increased the amount of plasma membrane-associated GluR4 [19].

Analytical, diagnostic and therapeutic context of PRKCG

• Western blot analyses showed an increased PKC-alpha level in terms of intensity and phosphorylation in the cell membrane, while neither PKC-beta nor PKC-gamma was activated upon hyposmotic challenge [25].
• Immunocytochemistry of brain sections supported these findings and revealed increased neuronal labelling for PKC alpha, PKC gamma and PKC lambda isoforms in neocortex of 16-month-old APPsw mice compared with nontransgenic littermates, with the increase being strongest for PKC gamma and PKC lambda isoforms [20].
• We screened exon 4 of the PRKCG gene in 882 SCA patients with undefined etiologies using denaturing high-performance liquid chromatography and subsequent direct sequencing [26].
• RESULTS: In homogenates from left and right ventricle, all isoforms except PKC-gamma and theta were detected by immunoblotting, with confirmation using a second antibody directed against a different epitope when possible [27].
• PC12 cells express PKC alpha and PKC beta, but not PKC gamma, as revealed by Northern-blot analysis [28].

References