Disease relevance of PRKX

• Adeno-associated virus type 2 Rep78 inhibition of PKA and PRKX: fine mapping and analysis of mechanism [1].
• We have isolated a gene, PKX1, by virtue of its position within the candidate region for chondrodysplasia punctata in Xp22 [2].
• This suggests that the PKX1 gene, besides harbouring a previously described hot-spot for illegitimate Xp/Yp-recombination, contains additional sequences predisposing to chromosomal breakage events [2].

High impact information on PRKX

• The human protein kinase X gene (PRKX) is a member of an ancient family of cAMP-dependent serine/threonine kinases here shown to be phylogenetically distinct from the classical PKA, PKB/Akt, PKC, SGK, and PKG gene families [3].
• These results suggest that the PRKX kinase may regulate epithelial morphogenesis during mammalian kidney development [3].
• PRKX kinase expression markedly activated migration of cultured renal epithelial cells in the presence of cAMP; this effect was blocked by cell treatment with the PKA inhibitor H89 and was not observed in PKA-transfected cells [3].
• Renal expression of the PRKX gene is developmentally regulated and restricted to the ureteric bud epithelium of the fetal metanephric kidney [3].
• Aberrant adult kidney expression of PRKX was found in autosomal dominant polycystic kidney disease [3].

Biological context of PRKX

• The unprecedented high sequence identity and identical orientation of PRKY to its homologous partner on the X chromosome, PRKX, explains the high frequency of abnormal pairing and subsequent ectopic recombination, leading to XX males and XY females and to the highest rate of recombination outside the pseudoautosomal region [4].
• FISH localization of the human Y-homolog of protein kinase PRKX (PRKY) to Yp11.2 and two pseudogenes to 15q26 and Xq12-->q13 [5].
• After the Yp inversion polymorphism, which is the preferential background for the PRKX/PRKY translocation in XX males and XY females, the OR-8p inversion is the second genomic polymorphism that confers susceptibility to the formation of common chromosome rearrangements [6].
• These results suggest that PRKX stimulates epithelial branching morphogenesis by activating cell migration and support a role for this kinase in the regulation of nephrogenesis and of collecting system development in the fetal kidney [7].
• In transfection assays, a PRKX expression vector was shown to be capable of activating CREB-dependent transcription [8].

Anatomical context of PRKX

• In addition, expression of PRKX kinase activated branching morphogenesis of Madin-Darby canine kidney cells in collagen gels even in the absence of cAMP and/or hepatocyte growth factor, an effect not seen with either PKA expression or expression of a mutant, kinase-inactivated PRKX [3].
• Among the blood cell lineages, the PRKX gene is specifically expressed in macrophages and granulocytes [9].
• Antisense inhibition of PRKX expression blocked terminal development in both the leukemic HL-60 cells and normal peripheral blood monocytes, implying that PRKX is a key mediator of macrophage and granulocyte maturation [9].
• We identified a gene coding for a protein kinase, protein kinase X (PRKX), which was expressed in the maturation-susceptible, but not in the resistant, cell line [9].
• We also studied the expression of the PRKX gene in 12 different human tissues and transformed cell lines and found that, among these tissues and cell types, the PRKX gene is expressed only in blood [9].

Associations of PRKX with chemical compounds

• This gene is highly homologous to a previously isolated gene from Xp22.3, PRKX, and represents a member of the cAMP-dependent serine threonine protein kinase gene family [4].
• The PRKX kinase belongs to a serine/threonine kinase family that is phylogenetically and functionally distinct from classical protein kinase A kinases [7].
• A cyclic adenosine monophosphate-regulated Ser/Thr kinase gene, protein kinase X (PRKX), has been associated with macrophage differentiation in human cells [10].

Regulatory relationships of PRKX

• We found that M-CSF and PKC-delta induced the expression of the PRKX murine homologue: PKA-related gene [10].

Other interactions of PRKX

• Abnormal XY interchange between a novel isolated protein kinase gene, PRKY, and its homologue, PRKX, accounts for one third of all (Y+)XX males and (Y-)XY females [4].
• As a consequence, Yp material, including SRY, has been replaced by terminal Xp sequences up to the PRKX gene [11].
• 3. In this region, two potential candidate genes, VCX-A and PRKX, were excluded by sequence analysis of the coding region in patients of the two reported FG families [12].
• First, PKX1 appears to encode a novel type of human protein kinase that is related to the catalytic subunit of cAMP-dependent protein kinases and has striking homology to the DC2 protein kinase from Drosophila melanogaster [2].

Analytical, diagnostic and therapeutic context of PRKX

• PCR and FISH analysis revealed that the mother carries a structurally altered Y chromosome that most likely resulted from an aberrant X-Y interchange between the closely related genomic regions surrounding the gene pair PRKX and PRKY on Xp22.3 and Yp11.2, respectively [11].
• Expression of PRKX activates cAMP-dependent renal epithelial cell migration and tubular morphogenesis in cell culture, suggesting that it might regulate branching growth of the collecting duct system in the fetal kidney [7].
• With the use of a mouse embryonic kidney organ culture system that recapitulates early kidney development in vitro, it is demonstrated that lentiviral vector-driven expression of a constitutively active, cAMP-independent PRKX in the ureteric bud epithelium stimulates branching morphogenesis and results in a 2.5-fold increase in glomerular number [7].

References