Disease relevance of pkc-1

• One of the candidate gene products, FEZ1 (fasciculation and elongation protein zeta-1), a protein kinase C (PKC)zeta-interacting protein homologous to the Caenorhabditis elegans synaptic transport protein UNC-76, was found to be up-regulated >30-fold in the resistant R3-2 line [1].

High impact information on pkc-1

• The predicted amino acid sequence revealed that the predicted tpa-1 protein sequence is highly similar to protein kinase C molecules from various animals, including man [2].
• Par6 and atypical protein kinase C are key players in the establishment of cell polarity [3].
• Molecular and pharmacological studies in vitro suggest that protein kinase C (PKC) family members play important roles in intracellular signal transduction [4].
• These findings confirm that the unc-13 gene product has binding sites similar to those of protein kinase C and may be a component of an alternative transduction pathway of the diacylglycerol signal to a different effector function in the nervous system [5].
• The defective phenotypes of PKC-3-depleted embryos are similar to those exhibited by mutants for par-3 and another par gene, par-6 [6].

Biological context of pkc-1

• DKF-1 phosphorylation and activation are unaffected when PKC activity is eliminated by inhibitors [7].
• Cells engaged in PKC1B gene transcription were identified in transgenic C. elegans that carry the lacZ gene under the regulation of the PKC1B promoter [8].
• Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-alpha [9].
• The presence of a C-terminal src homology 3 (SH3) domain and its phosphorylation by casein kinase 2 (CK2) and protein kinase C (PKC) imply a role in signaling [10].
• During a large-scale screen of a human fetal brain cDNA library, a novel human gene GNB2L1 encoding a novel RACK (receptor of activated protein kinase C) protein was isolated and sequenced [11].

Anatomical context of pkc-1

• The expression of pkc-1 seems to be specific to neurons, while that of pkc-2 is detected in several types of cells including neurons and muscle cells [12].
• The intracellular localization of PKC1B and the enzyme's differential solubility in ionic and nonionic detergents suggest that the kinase is associated with membranes and the cytoskeleton [8].
• Staining for beta-galactosidase revealed PKC1B promoter activity exclusively in sensory neurons and interneurons [8].
• Immunofluorescence microscopy disclosed that the PKC1B polypeptide is located in the processes (axons and dendrites) and perinuclear regions of approximately 75 neurons that constitute the sensory circuitry of the nematode [8].
• Hydroxyapatite column chromatography showed only one peak of PKC activity with histone H1 and myelin basic protein as substrates [13].

Associations of pkc-1 with chemical compounds

• Ca(2+)-dependent activation of nematode PKC was observed in the presence of phosphatidylserine [13].
• These results suggest that PKC-dependent signaling pathways may promote nicotine adaptation via regulation of nicotinic receptor synthesis or degradation [14].
• Structure-activity analysis revealed significant but modest differences between recombinant cysteine-rich regions of Unc-13 and PKC delta [15].
• Inhibition of insulin-induced glucose uptake by atypical protein kinase C isotype-specific interacting protein in 3T3-L1 adipocytes [16].
• Calphostin C, a compound described as a selective inhibitor of PKC, was also able to inhibit [3H]PDBu binding to Unc-13, suggesting that this inhibitor is not able to distinguish between different classes of phorbol ester receptors [15].

Regulatory relationships of pkc-1

• Finally, PKC1A and PKC1B mRNA levels are differentially regulated by phorbol esters in a process that may involve the participation of another PKC isoform that is analogous to mammalian PKC delta [17].

Analytical, diagnostic and therapeutic context of pkc-1

• C. elegans provides an excellent model system for molecular dissection of the cellular signaling pathways involving PKC [12].
• Endogenous UNC5H1 and PICK1 coimmunoprecipitate from extracts of cultured hippocampal neurons and P4 cortices, and immunohistochemistry shows that UNC5H1, PICK1, and PKC are all present in growth cones [18].
• The gene was deduced to code for a protein kinase C (PKC) homologue by molecular cloning [19].
• Ablation of PKC3 function by microinjection of antisense RNA into oocytes yields disorganized, developmentally arrested embryos [20].
• Animal models in the study of protein kinase C isozymes [21].

References