title: Nucleoside-diphosphate kinase-mediated signal transduction via histidyl-aspartyl phosphorelay systems in Escherichia coli.
abstract: Nucleoside-diphosphate kinase (NDP kinase), a key enzyme in nucleotide metabolism, is also known to be involved in growth and developmental control and tumor metastasis suppression. Interestingly, we find that coexpression of NDP kinase with Taz1, a Tar/EnvZ chimera, in the absence of its native signal, can activate a porin gene ompC-lacZ expression in Escherichia coli. Further studies show that NDP kinase can act as a protein kinase to phosphorylate histidine protein kinases such as EnvZ and CheA which are members of the His-Asp phosphorelay signal transduction systems in E. coli. Instead of ATP, the exclusive phosphodonor for histidine kinases, GTP can be utilized in vitro in the presence of NDP kinase to phosphorylate EnvZ and CheA, which then transfer the phosphoryl group to OmpR and CheY, the respective response regulators. The direct involvement of GTP for the phosphorylation of EnvZ through NDP kinase was further demonstrated by the use of a mutant EnvZ, which lost ability to be autophosphorylated with ATP. Phospho-OmpR thus formed can bind specifically to an ompF promoter sequence. These results suggest that NDP kinase may play a physiological role in signal transduction.
authors.affiliation: Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Lu
authors.forename: H
authors.initials: H
authors.lastname: Park
authors.forename: L A
authors.initials: LA
authors.lastname: Egger
authors.forename: M
authors.initials: M
authors.lastname: Inouye
mesh_terms: D001224:Aspartic Acid / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D000071677:Histidine Kinase; D008565:Membrane Proteins / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D009097:Multienzyme Complexes; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases; D015398:Signal Transduction
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D009097:Multienzyme Complexes; D010750:Phosphoproteins; C072091:Taz1 protein, E coli; C000607606:cheY protein, E coli; D001224:Aspartic Acid; D006639:Histidine; D006160:Guanosine Triphosphate; D011494:Protein Kinases; D000071677:Histidine Kinase; C000607608:cheA protein, E coli; C057843:envZ protein, E coli; D009701:Nucleoside-Diphosphate Kinase; D010749:Phosphoprotein Phosphatases