Disease relevance of PRKG1

• The association between C2276T polymorphism in PRKG1 gene and obesity was tested using linear regression analysis [1].
• To determine whether Langerhans' histiocytosis is a polyclonal reactive disease or a clonal disorder, we used X-linked polymorphic DNA probes (HUMARA, PGK, M27 beta[DXS255], and HPRT) to assess clonality in lesional tissues and control leukocytes from 10 female patients with various forms of the disease [2].
• Recombination frequencies of 0%-4% were found between choroideremia and five markers (PGK, DXS3, DXYS12, DXS72, and DXYS1) located in Xq13-22 [3].
• We used human immunodeficiency virus type-1 (HIV-1)-based vectors expressing enhanced green fluorescent protein (EGFP) driven by different promoters (CMV, MPSV, or PGK) and investigated their ability to transduce human T- and B-cell lines, as well as resting or activated primary peripheral and umbilical cord blood lymphocytes [4].
• Specimens from 10 fibroadenomas and 5 phyllodes tumors heterozygous for the BstXI polymorphism of PGK gene were subjected to clonal analysis [5].

High impact information on PRKG1

• Analysis of mouse-human hybrids with the relevant chromosome provides evidence that the derepressed locus is on the inactive X, and that reactivation is not extensive (the PGK locus is not derepressed) [6].
• We therefore analysed X-chromosome inactivation patterns with differential methylation patterns of heterozygotes for three DNA probes, HPRT, PGK, and M27 beta, in leukaemic patients and normal controls [7].
• Data obtained using this assay correlated substantially with those obtained using the PGK, HPRT, and M27 beta probes, which detect X inactivation patterns by Southern blot analysis [8].
• The content of mRNA in the variant fibroblasts was compared to that of normal cells by the semiquantitative dot hybridization method, and, more accurately, by the liquid hybridization method, using a human PGK cDNA as a probe [9].
• Microsatellite polymerase chain reaction (PCR) and PCR analysis of PGK gene methylation have been used to study highly purified populations of peripheral blood cells [10].

Chemical compound and disease context of PRKG1

• OBJECTIVE: To investigate whether genetic variation in the cyclic GMP-dependent protein kinase gene (PRKG1) is associated with obesity [1].

Biological context of PRKG1

• PRKG1 is a single-copy gene consisting of 19 exons encompassing at least 220 kb [11].
• The aim of this study was to investigate for the presence of linkage disequilibrium between the protein kinase G gene (PRKG1) and adult ADHD in a sample of nuclear families [12].
• Southern blot analysis suggested that human cGKIalpha and cGKIbeta are generated by alternative splicing of a single gene assigned to chromosome 10 [13].
• In humans, cGKIbeta cDNA was isolated, but the full structure and tissue-specific gene expression of cGKIalpha have not been determined [13].
• In situ hybridization analyses using 3H-labeled cDNA and genomic DNA probes for the human type I cGK to human metaphase chromosomes supported the somatic cell hybrid data and indicated that the gene (PRKG1B; protein kinase, cGMP-dependent) maps to 10p11.2----q11.2 [14].

Anatomical context of PRKG1

• In contrast, human cGKIbeta mRNA (7.0 kb) was detected abundantly only in the uterus [13].
• Three different second-generation lentiviral self-inactivating vectors containing CMV, EF1alpha and PGK promoter, respectively, and all carrying the exogenous GFP gene, were compared for expression in human B-cell precursor ALL blasts [15].
• Substituting the CAG promoter for PGK in lentiviral constructs enhanced transgene expression in DC and EBV-B cells, amplifying T cell recognition [16].
• Plasmid DNA containing factor VIII or factor IX minigenes and driven by three human cellular promoters (albumin, factor IX, PGK) or the strong viral promoter RSV-LTR were electroporated into TE671 and HepG2 cell lines, and clotting factor levels were determined by ELISA [17].
• The Ad5F35-GFP vector-mediated gene transfer efficiency was compared with a fiber non-modified Ad5-GFP vector, which also encodes the GFP gene under the control of the PGK promoter [18].

Associations of PRKG1 with chemical compounds

• Mutation of these four serines to alanine showed that cGKIbeta-dependent phosphorylation of Ser(696) is necessary to decrease calcium release from InsP(3)-sensitive stores [19].
• For the type I cGMP-dependent protein kinases (cGKIalpha and cGKIbeta), a high affinity interaction exists between the C2 amino group of cGMP and the hydroxyl side chain of a threonine conserved in most cGMP binding sites [20].
• Immunological analysis of cyanogen bromide digests of SmPGK with monoclonal antibodies that recognize SmPGK but not human PGK identifies a B-cell epitope on a 12.2-kDa fragment represented by amino acids 61 to 174 [21].
• Human PGK demonstrated catalytic efficiencies in the 10(4)-10(5)M(-1)s(-1) range for purine ribo-, deoxyribo- and dideoxyribonucleotide derivatives, either in D- or L-configuration [22].
• In the present work, we extended the enzymatic study of human PGK specificity to purine and pyrimidine nucleotide derivatives in both D- and L-configuration [22].

Physical interactions of PRKG1

• IRAG is present in a macromolecular complex with the InsP(3) receptor type I (InsP(3)RI) and cGKIbeta [19].

Other interactions of PRKG1

• The protein kinase cGMP-dependent, type I (PRKG1) and the TBP genes were expressed at common abundance and exhibited the lowest variability among the cell specimens [23].
• These results show that cGMP induced reduction of cytosolic calcium concentrations requires cGKIbeta and phosphorylation of Ser(696) of IRAG [19].
• Finally, we present evidence that the dominant negative properties of this truncation mutant are specific to cGKII when compared with cAMP-dependent protein kinase Calpha and cGKIbeta [24].

Analytical, diagnostic and therapeutic context of PRKG1

• In four patients, three of whom were already studied by Southern analyses of genomic DNA and one in whom there were insufficient amounts of DNA, polymerase chain reaction (PCR)-based clonal analysis was performed with primer pairs flanking the BstXI polymorphism on the PGK gene [25].
• We used WAS-/- mice to test the efficacy of a gene therapy approach based on nonlethal irradiation followed by transplantation of WAS-/- HSCs transduced with lentiviral vectors encoding the WAS protein (WASP) from either the ubiquitous PGK promoter or the tissue- specific WAS promoter [26].
• Thus, during natural infection antibodies that cross-react with human PGK are not produced; however, as a result of active immunization with an intact conserved molecule, such cross-reacting antibodies are produced [21].
• RT-PCR analysis identified this aberrant transcript as arising from the antisense strand of the PGK promoter [27].

References