Identification of two active functional domains of human adenylate kinase 5.

Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.
FEBS letters (Impact Factor: 3.54). 09/2009; 583(17):2872-6. DOI: 10.1016/j.febslet.2009.07.047
Source: PubMed

ABSTRACT A full length cDNA that partially corresponded to human adenylate kinase 5 (AK5) was identified and shown to encode for two separate domains. The full length protein could be divided in two distinct functional domains, a previously unidentified domain of 338 amino acids and a second domain of 198 amino acids that corresponded to the protein characterized as AK5, now called AK5p2. The first domain, AK5p1, phosphorylated AMP, CMP, dAMP and dCMP with ATP or GTP as phosphate donors similarly to AK5p2. Our data demonstrate that human AK5 has two separate functional domains and that both have enzymatic activity.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Adenylate kinase isozyme 4 (AK4) belongs to a family of nucleotide monophosphate kinases involved in energy metabolism. Recently, AK4 was reported to play a role in protection from stress: In HEK293 cells, hypoxia increases AK4 expression but does not affect proliferation or viability, while RNA interference (RNAi) directed against AK4 inhibits proliferation and promotes death. By contrast, we show here that HepG2 cells showed much higher AK4 levels, which decreased under hypoxia along with markedly reduced cell proliferation and increased cell death. Nevertheless, RNAi directed against AK4 inhibited cell proliferation and caused death in both cell types, although cell cycle parameters were affected only in HepG2 cells. Hence reductions of AK4 levels were always associated with cell death. These results extend the notion of a stress-protective function of AK4 to a novel physiological context and show that AK4-mediated stress protection is not limited to one particular death scenario. Our data also allow the hypothesis that the different basal AK4 levels reflect different basal stress levels, causing alternative responses to additional stress.
    Archives of Biochemistry and Biophysics 03/2013; · 3.04 Impact Factor
  • Value in Health 11/2008; 11(6). · 2.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adenine nucleotides are involved in a variety of cellular metabolic processes, including nucleic acid synthesis and repair, formation of coenzymes, energy transfer, cell and ciliary motility, hormone secretion, gene expression regulation and ion-channel control. Adenylate kinases are abundant phosphotransferases that catalyze the interconversion of adenine nucleotides and thus regulate the adenine nucleotide ratios in different intracellular compartments. Nine different adenylate kinase isoenzymes have been identified and characterized so far in human tissues, named AK1 to AK9 according to their order of discovery. Adenylate kinases differ in molecular weight, tissue distribution, subcellular localization, substrate and phosphate donor specificity and kinetic properties. The preferred substrate and phosphate donor of all adenylate kinases are AMP and ATP respectively, but some members of the family can phosphorylate other substrates and use other phosphate donors. In addition to their nucleoside monophosphate kinase activity, adenylate kinases were found to possess nucleoside diphosphate kinase activity as they are able to phosphorylate both ribonucleoside and deoxyribonucleoside diphosphates to their corresponding triphosphates. Nucleoside analogues are structural analogues of natural nucleosides, used in the treatment of cancer and viral infections. They are inactive prodrugs that are dependent on intracellular phosphorylation to their pharmacologically active triphosphate form. Novel data presented in this review confirm the role of adenylate kinases in the activation of deoxyadenosine and deoxycytidine nucleoside analogues.
    The international journal of biochemistry & cell biology 04/2014; · 4.89 Impact Factor

Full-text (2 Sources)

Available from
May 30, 2014