Identification of a molecular target for the Yersinia protein kinase A

Pathogenic bacteria of the genus Yersinia employ a type III secretion system to inject bacterial effector proteins directly into the host cytosol. One of these effectors, the Yersinia serine/ threonine protein kinase YpkA, is an essential virulence determinant involved in host actin cytoskeletal rearrangements and in inhibition of phagocytosis. Here we report that YpkA inhibits multiple G alpha q signaling pathways. The kinase activity of YpkA is required for G alpha q inhibition. YpkA phosphorylates Ser47, a key residue located in the highly conserved diphosphate binding loop of the GTPase fold of G alpha q. YpkA-mediated phosphorylation of Ser47 impairs guanine nucleotide binding by G alpha q. Y. pseudotuberculosis expressing wild-type YpkA, but not a catalytically inactive YpkA mutant, interferes with G alpha q-mediated signaling pathways. Identification of a YpkA-mediated phosphorylation site in G alpha q sheds light on the contribution of the kinase activity of YpkA to Yersinia pathogenesis.