Disease relevance of Galk1

• Activity of thymidylate synthetase, thymidine kinase and galactokinase in primary and xenografted human colorectal cancers in relation to their chromosomal patterns [1].
• In humans, GK deficiency results in congenital cataracts due to an accumulation of galactitol within the lens [2].
• To generate an animal model for MODY we have expressed in transgenic mice a GK antisense RNA with a ribozyme element under control of the insulin promoter [3].
• At moderate doses of dGalF, 19F-NMR spectroscopy in vivo or in vitro could be used to pinpoint defects of the enzymes that cause galactosemia, i.e. of galactokinase, uridyltransferase, or 4-epimerase [4].

High impact information on Galk1

• A synteny between myosin heavy chain and two unrelated markers, thymidine kinase and galactokinase, was found to be preserved in the rodent and human genomes [5].
• Phosphorylation of glucose to glucose 6-phosphate by glucokinase (GK; EC 2.7.1.2) serves as a glucose-sensing mechanism for regulating insulin secretion in beta cells [3].
• This suggests that the distance between the tk and galk genes in the Chinese hamster genome may be smaller than was previously thought [6].
• In addition, both galactose and galactitol accumulated in tissues of GK-deficient mice [2].
• Three plasmids, each containing a galactokinase K (galK) gene, were used to transform galK- Chinese hamster cells [7].

Chemical compound and disease context of Galk1

• Surprisingly, the GK-deficient animals did not form cataracts even when fed a high galactose diet [2].

Biological context of Galk1

• The TK-/- mutant frequency of strain LY-R83, which is monosomic for chromosome 11 and thus hemizygous for the tk and gk genes, was only 50% of the mutant frequency of strain LY-R16 which is heterozygous for the tk gene [8].
• The possibility that the loss of GLK activity is not indicative of LOH at the Glk gene under the conditions of the present experiments is discussed [9].
• The frequency of mutants losing GLK activity was low, particularly in cells irradiated in the S or G2/M phases [9].
• From the pattern of cotransfer, a tentative gene ordering of CENTROMERE-GALK-TK1-GAA on human chromosome 17 was deduced [10].
• In screening the sequences of the genes involved in lactose assimilation, we found that the galactokinase gene Glk contains four potential Egr-1 binding sites in its proximal promoter [11].

Anatomical context of Galk1

• Two linked human genes which code for the expression of cytosol thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) and galactokinase (ATP:D-galactose 1-phosphotransferase, EC 2.7.1.6) have been cotransferred via purified metaphase chromosomes from the human lymphoblastoid cell line WI-L2a, into mouse L-cells [B82 and LM(TK-)] [12].
• We have studied the expression of mouse galactokinase in human-mouse somatic cell hybrids segregating mouse chromosomes [13].
• In this study we investigated the expression of primate galactokinase in somatic cell hybrids between a thymidine kinase-deficient mouse cell line and two different primate cell lines, one of which was derived from African green monkey kidney cells and the other from chimpanzee fibroblasts [14].

Associations of Galk1 with chemical compounds

• As expected, galactose was very poorly metabolized in GK-deficient mice [2].
• The chimpanzee thymidine kinase and galactokinase genes were assigned to PTR 19 (HS 17), further confirming the homology to HS 17 [15].
• When these clones were backselected in medium containing 5-bromodeoxyuridine, both this chromosome and the monkey galactokinase activity were lost [14].
• There was no difference in sensitivity to the G-kinase I activator 8-para-chlorophenylthio-cGMP or to cromakalim [16].
• The functional activity of cyclic GMP-dependent protein kinase (G-kinase) and PDE V was also unchanged, suggesting that sGC is the site of up-regulation [17].

Other interactions of Galk1

• The frequency of mutants with LOH at both Tk1 and D11Nds7 with no loss of GLK activity was high in all cell populations: There was no significant difference in the observed frequency of these mutants between the populations [9].
• Developmental regulation of galactokinase in suckling mouse liver by the Egr-1 transcription factor [11].
• Umph-2 cosegregated with the mouse galactokinase (Glk) gene in 23 of the 24 hybrids and showed at least four discordances with all other mouse marker isozymes examined [18].
• Analysis of 15 other biochemical markers located on 12 of the mink chromosomes revealed the activities of mink galactokinase (a syntenic marker) in 5 transformed clones, and that of mink aconitase-1 (the marker of mink chromosome 12) in 1 clone [19].
• We found that type II cGMP-dependent protein kinase (G-kinase), which is widely expressed in the brain, mediated NO- and cGMP-induced activation of the fos promoter in cells of neuronal and glial origin; the enzyme was ineffective in regulating gene expression in fibroblast-like cells [20].

Analytical, diagnostic and therapeutic context of Galk1

• In an attempt to make a galactosemic animal model, we cloned the mouse GK gene (Glk1) and disrupted it by gene targeting [2].
• They provide an animal model for studying the interaction of such factors with the reduced islet GK activity [3].
• Consequently, [18F]FDT is expected to be a new radiopharmaceutical for the measurement of galactokinase activity by positron emission tomography [21].
• The 42 kDa protein band was detected to be phosphorylated by G kinase on SDS-PAGE [22].

References