A distinctive role for the Yersinia protein kinase: actin binding, kinase activation, and cytoskeleton disruption.
The bacterial pathogens of the genus Yersinia deliver several virulence factors into target cells using a type III secretion system. We demonstrate that Yersinia protein kinase A (YpkA), an essential bacterial virulence factor, is produced as an inactive serine/threonine kinase. The inactive kinase is activated within the host cell by a cytosolic eukaryotic activator. Using biochemical purification techniques, we demonstrate that actin is a cellular activator of YpkA. This stimulation of YpkA kinase activity by actin depends on the presence of the C-terminal twenty amino acids of YpkA, because deletion of these 20 aa not only obliterates YpkA activity, but it also destroys the interaction between YpkA and actin. Activated YpkA functions within cultured epithelial cells to disrupt the actin cytoskeleton. The disruption of the actin cytoskeleton by YpkA would be expected to inhibit macrophage function and phagocytosis of Yersinia.
Juris
S J
SJ
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109-0606, USA.
Rudolph
A E
AE
Huddler
D
D
Orth
K
K
Dixon
J E
JE
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001426:Bacterial Proteins; D002417:Cattle; D002460:Cell Line; D048429:Cell Size; D003067:Coenzymes / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics; D014162:Transfection; D015008:Yersinia enterocolitica / Q000201:enzymology* / Q000472:pathogenicity*
D000199:Actins; D001426:Bacterial Proteins; D003067:Coenzymes; C079893:ypkA protein, Yersinia; D017346:Protein Serine-Threonine Kinases