Protein tyrosine kinases in bacterial pathogens are associated with virulence and production of exopolysaccharide.
In eukaryotes, tyrosine protein phosphorylation has been studied extensively, while in bacteria, it is considered rare and is poorly defined. We demonstrate that Escherichia coli possesses a gene, etk, encoding an inner membrane protein that catalyses tyrosine autophosphorylation and phosphorylation of a synthetic co-polymer poly(Glu:Tyr). This protein tyrosine kinase (PTK) was termed Ep85 or Etk. All the E.coli strains examined possessed etk; however, only a subset of pathogenic strains expressed it. Etk is homologous to several bacterial proteins including the Ptk protein of Acinetobacter johnsonii, which is the only other known prokaryotic PTK. Other Etk homologues are AmsA of the plant pathogen Erwinia amylovora and Orf6 of the human pathogen Klebsiella pneumoniae. These proteins are involved in the production of exopolysaccharide (EPS) required for virulence. We demonstrated that like Etk, AmsA and probably also Orf6 are PTKs. Taken together, these findings suggest that tyrosine protein phosphorylation in prokaryotes is more common than was appreciated previously, and that Etk and its homologues define a distinct protein family of prokaryotic membrane-associated PTKs involved in EPS production and virulence. These prokaryotic PTKs may serve as a new target for the development of new antibiotics.
Ilan
O
O
Department of Molecular Genetics and Biotechnology, The Hebrew University Faculty of Medicine, PO Box 12272, Jerusalem 91120, Israel.
Bloch
Y
Y
Frankel
G
G
Ullrich
H
H
Geider
K
K
Rosenshine
I
I
D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D003429:Cross Reactions; D004755:Enterobacteriaceae / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D007425:Intracellular Membranes / Q000201:enzymology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000276:immunology / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014774:Virulence
D000906:Antibodies; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C120614:Etk protein, E coli; D008565:Membrane Proteins; D010750:Phosphoproteins; D011135:Polysaccharides, Bacterial; D019000:Phosphotyrosine; C492367:BMX protein, human; D011505:Protein-Tyrosine Kinases