Disease relevance of PCTK3

• An adenoviral vector encoding PCTAIRE3 (Ad-PCTAIRE3) induced growth arrest and killed a minor proportion of the glioma cells [1].

Psychiatry related information on PCTK3

• The regulation of tau phosphorylation by PCTAIRE 3: implications for the pathogenesis of Alzheimer's disease [2].

High impact information on PCTK3

• The resurgence of cell cycle proteins is an important mechanism in Alzheimer's disease (AD), and we propose that PCTAIRE 3 is a PHF-associated kinase that modulates tau phosphorylation [2].
• PCTAIRE 3 is a member of the PCTAIRE subfamily of cdc2-related serine/threonine protein kinases [3].
• Primary sequence comparisons between different cdc2-related serine/threonine protein kinases reveal that these proteins are most heterogeneous in their N-terminal domains and the PCTAIRE subfamily is further diversified by the presence of isoforms within this region [3].
• The major transcript of PCTAIRE 3, designated PCTAIRE 3a, has an open reading frame that is 474 amino acids in length [3].
• Expression of PCTAIRE 3b was limited to several subcortical nuclei of the basal gangli and the spinal cord and substantial levels of this transcript were not evident outside of the central nervous system [3].

Biological context of PCTK3

• To analyze the genomic structure and chromosomal location of the PCTAIRE-1 and -3 genes, we isolated human cosmid clones for each gene by screening a human genomic library with murine PCTAIRE cDNA probes [4].
• These clones were confirmed to encode authentic PCTAIRE genes by the detection of exon-intron structures and the coincidence of the nucleotide sequence of exons to that of the published human cDNAs [4].

Anatomical context of PCTK3

• In an immunocytochemical experiment, immunoreactivity for PCTAIRE 2 was detected in the cell bodies and extended neurites of neurons, but not in astrocytes [5].
• Within the brain, PCTAIRE 2 was concentrated in the neuronal layers of the hippocampus and olfactory bulb, which mostly consist of post-mitotic neurons [5].

Regulatory relationships of PCTK3

• Altogether, these data identify PCTAIRE3 as one novel growth-inhibitory and death-inducing p53 response gene and suggest that changes in the expression of specific target genes contribute to the superior anti-glioma activity of CTS-1.Cancer Gene Therapy (2006) 13, 469-478. doi:10.1038/sj.cgt.7700917; published online 4 November 2005 [1].

Analytical, diagnostic and therapeutic context of PCTK3

• Overexpression of PCTAIRE 3 in cell culture suggests that the protein acts indirectly to stimulate phosphorylation at the pT231 and pS235 sites on tau, residues that are modified early in the process of AD pathogenesis [2].
• An immunoprecipitation assay revealed that the PCTAIRE 2 was associated with Ser/Thr-phosphorylating activity for histone H1, and that its activity depended on association with a regulatory partner that can be released under high-salt conditions [5].
• Epitope mapping reveals three distinct classes of PCTAIRE 3 antibodies that recognize different sites within an immunodominant region of the N-terminal domain of the protein [6].
• Immunoblotting of transfected cells reveals that all of the antibodies recognize both isoforms of the PCTAIRE 3 kinase [6].

References