High impact information on AK2

• This residual activity is consistent with the existence of genetically independent AK isozyme, AK2, which is known to exist in these tissues [1].
• The minute amount of residual activity in erythrocytes could represent a small amount of the AK2 isozyme, which has not been thought to be present in erythrocytes, or the activity of erythrocyte guanylate kinase with AMP substituting as substrate for GMP [1].
• We observed a caspase-independent, simultaneous release of cytochrome c, Smac, Omi, and adenylate kinase-2 [2].
• The contribution of the GPIbalpha receptor to platelet activation induced by the anti-beta2GPI antibody-beta2GPI complex was assessed by observing the influence of 2 anti-GPIbalpha antibodies (AK2 and SZ2) directed against distinct epitopes [3].
• Activation of Rap1B induced by thrombin was not affected by preincubation of platelets with the anti-GPIbalpha monoclonal antibody AK2 in the absence of ADP scavengers or a P2Y12 antagonist but was totally abolished when secreted ADP was neutralized or after blockade of the P2Y12 receptor [4].

Biological context of AK2

• However, three isozymes, AK1, AK2 and AK3, have been characterized in mammalian cells and shown to be localized in the cytosol, mitochondrial intermembrane space and mitochondrial matrix, respectively, and it is unknown which one of these isozymes accumulates in the cytosol during apoptosis [5].
• Somatic cell hybrid studies indicate that the AK3 locus is not syntenic with that of AK2 (chromosome 1) [6].
• The observed gene frequencies are PGM21 = 0.280; AK2 = 0.030; ADA2 = 0.091; ACPa = 0.297; ACPb = 0.647; ACPc = 0.056 [7].
• These results suggested the presence of the tissue-specific gene-expression including post-transcriptional regulation in expression of the AK2 gene [8].
• We isolated two kinds of cDNAs encoding human adenylate kinase (AK) isozyme 2 from a HeLa cell cDNA library using bovine AK2 cDNA as a probe [8].

Anatomical context of AK2

• These tissue-specific expressions of the AK isozymes in human might suggest the presence of organ-specific regulation of the AK2 gene including a post-transcriptional control in skeletal muscle [9].
• The subcellular compartmentalization of the isoenzymes of ATP:AMP phosphotransferase (adenylate kinase) was analyzed in HeLa cells, RAG cells, and RAG-human hybrids that express human AK-2 [10].
• In HeLa cells and in the hybrids, human AK-2 was present in a mitochemical fraction prepared from cell extracts and in mitochondria purified by density gradient centrifugation [10].
• Northern blot analysis demonstrated that AK2 mRNA is strongly expressed in liver, heart, skeletal muscle and pancreas, and moderately in kidney, placenta and brain, and weakly in lung [8].
• Subcellular distribution, sulfhydryl inhibitor, and substrate specificity studies support the hypothesis that the mitochondrial adenylate kinase (AK2) is a major route of cellular activation of these compounds in human lymphocytes [11].

Associations of AK2 with chemical compounds

• However, AK1 showed a greater affinity than AK2 to anti-lobster arginine kinase antibodies, particularly to those raised against the native enzyme [12].
• The overall gene frequencies were as follows: Hp1, 0.21; Gc1F, 0.34; Gc1S, 0.36; Gc2, 0.30; TfC1, 0.66; TfC2, 0.26; TfC3, 0.001; TfD, 0.06; GLO1, 0.21; PGI2, 0.04; AK2, 0.01; PGM1+, 0.80; PGM1-, 0.06; PGM2+, 0.11 and PGM2-, 0.02 [13].
• 3. AK1 had slower electrophoretic mobility at pH 8.3 towards the anode, higher lysine content, lower glutamate content, lower Km for L-arginine and higher Km for Mg(2+)-ATP than AK2 [12].
• Aggregation supported by vWF unlike fibrinogen supported aggregation was almost completely inhibited not only by GPIIb-IIIa antagonists (F(ab')2 fragment of blocking anti-GPIIb-IIIa antibody CRC64 and peptidomimetic aggrastat) but also by anti-GPIb blocking antibody AK2 [14].

Regulatory relationships of AK2

• In addition, AK-1 was found to be expressed independently of AK-2 [15].
• Interestingly, we show that e.g., adenylate kinase 2 is highly upregulated by IFN-alpha and IL-15 stimulation in NK-92 cells [16].

Other interactions of AK2

• The other type (AK2B) encoded the same sequence as AK2 except for the COOH terminus [17].
• The distribution of red cell enzymes showed Mongoloid characteristics with low PGDC, AK2, ESD1, GLO1, and higher pa [18].
• AK2 is expressed in the intermembrane space, while AK3 and AK4 are localized in the mitochondrial matrix [19].
• Assignment of ADA, ITPA, AK1, and AK2 to Chinese hamster chromosomes. Genetic and structural evidence for the conservation of mammalian autosomal synteny [20].
• Further, there is no masking of the adenylate kinase 2 band as a result of the use of a reducing agent, and carbonic anhydrase II is resolved without interference from hemoglobin as has been observed with other multisystem methods [21].

Analytical, diagnostic and therapeutic context of AK2

• Western blot analysis of AK isozymes in human heart and skeletal muscle revealed that AK2 protein was found only in heart, whereas AK1 was detected in both tissues [9].
• The patient's enzyme migrated approximately half-way between the AK 1 and AK 2 position on starch-gel electrophoresis [22].

References