Disease relevance of PGK2

• In an attempt to determine the susceptibility of spermatocytes to malignant transformation by simian virus 40 (SV40) large tumour antigen (TAg), transgenic mice harbouring a chimeric gene composed of the SV40 TAg gene fused to the 1.4 kb promoter sequence of the human phosphoglycerate kinase 2 (PGK2) gene were generated [1].

High impact information on PGK2

• Both the unusual conservation of function in this processed PGK-2 gene and its tissue-specific expression in spermatogenesis are best explained as a compensatory response to the inactivation of the X-linked PGK-1 gene in spermatogenic cells before meiosis [2].
• PGK-2 is an autosomal gene expressed in a tissue-specific manner exclusively in the late stages of spermatogenesis [2].
• In the present study, a molecular analysis of a human genomic clone of PGK-2 originally isolated by Szabo et al. has revealed that this autosomal sequence completely lacks introns and contains characteristics of a processed gene, or 'retroposon', including the remnants of a poly(A)+ tail and bounding direct repeats [2].
• In addition, GRTH participated in the nuclear export of RNA messages (PGK2, tACE, and TP2) in a gene-specific manner [3].
• PGKBP-3 Tg mice showed the most marked reduction in bone density [4].

Biological context of PGK2

• We examined DNA methylation throughout the endogenous murine testis-specific phosphoglycerate kinase (Pgk2) gene and in human PGK2 promoter/CAT reporter transgenes in mouse spermatogenic cells before, during, and following the period of active transcription of this gene [5].
• The PGK2 gene is expressed in a strictly tissue-specific manner in meiotic spermatocytes and postmeiotic spermatids during spermatogenesis in eutherian mammals [6].
• We have also analyzed the amino acid sequence and protein characteristics of the PGK-2 isozyme deduced from this cDNA and compared them with that of the human PGK-1 isozyme to show that known structural and functional motifs are conserved in both proteins [7].
• Expression of the PGK-2 gene may function solely to compensate for repressed expression of the PGK-1 gene due to X-chromosome inactivation in spermatocytes [7].
• Although mature PGK-2 mRNA is present in meiotic cells it is not actively translated until after meiosis has been completed [8].

Anatomical context of PGK2

• Alternative y, the PGK-2 gene could encode an isozyme with unique characteristics that are beneficial to spermatozoa [7].
• We have isolated a cDNA of the human PGK-2 gene and used this as probe to demonstrate that transcription of this gene in spermatocytes and spermatids coincides with a period of repressed transcription of the X-linked PGK-1 gene during spermatogenesis in the human testis [7].
• No PGK-2 mRNA activity was observed in the cytoplasmic RNA from primitive type A spermatogonia or prepubertal Sertoli cells [8].
• As an example for this approach, a new murine germ cell line (GC-4spc) was established using a vector construct that contains the SV40 large T antigen and the neomycin phosphotransferase II gene under the control of the SV40 early promoter and a spermatocyte-specific promoter for human phosphoglycerate kinase 2, respectively [9].
• Furthermore, TSPY (human testis-specific protein, Y-encoded) and PGK2 (human phosphoglycerate kinase 2) promoter regions showed different transcriptional activities in the GC-4spc cell line compared with the spermatogonia-derived cell line GC-1spg [9].

Associations of PGK2 with chemical compounds

• The responses to a glucose challenge were significantly increased in both Tg strains: area under the glucose curve = 1,824 +/- 65 and 1,910 +/- 115 vs. 1,590 +/- 67 mmol. l(-1). min for CMVBP-3, PGKBP-3, and Wt mice, respectively [10].
• Two 3-phosphoglycerate kinase genes (pgk1 and pgk2) were cloned from Rhizopus niveus [11].
• Using double labeling with tetracycline, we demonstrated that pericortical and endocortical mineral apposition rate was significantly reduced in PGKBP-3 Tg mice compared with Wt mice [4].

Other interactions of PGK2

• PGK1 is an X-linked house-keeping enzyme, and PGK2 is a mainly testis-specific enzyme under autosomal control [12].
• Three pairs of primers were used for amplification of male germ cell-specific genes (DAZ, transcribed in male germ cells; PGK2, in late spermatocytes and spermatids; protamine-2, in spermatids) as molecular markers [13].

Analytical, diagnostic and therapeutic context of PGK2

• The mRNA activity for PGK-2 from the polysomal and nonpolysomal fractions of pachytene primary spermatocytes or round spermatids has been assayed by cell-free translation with the polypeptide products monitored by immunoprecipitation, followed by one-dimensional or two-dimensional electrophoresis and fluorography [8].

References