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 fac tors into target cells using a type III secretion system. We demonstrate th at Yersinia protein kinase A (YpkA), an essential bacterial Virulence facto r, is produced as an inactive serine/threonine kinase. The inactive kinase is activated within the host cell by a cytosolic eukaryotic activator, Usin g biochemical purification techniques, we demonstrate that actin is a cellu lar activator of YpkA, This stimulation of YpkA kinase activity by actin de pends 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 de stroys the interaction between YpkA and actin. Activated YpkA functions wit hin cultured epithelial cells to disrupt the actin cytoskeleton. The disrup tion of the actin cytoskeleton by YpkA would be expected to inhibit macroph age function and phagocytosis of Yersinia.