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 Galphaq signaling pathways. The kinase activity of YpkA is required for Galphaq inhibition. YpkA phosphorylates Ser47, a key residue located in the highly conserved diphosphate binding loop of the GTPase fold of Galphaq. YpkA-mediated phosphorylation of Ser47 impairs guanine nucleotide binding by Galphaq. Y. pseudotuberculosis expressing wild-type YpkA, but not a catalytically inactive YpkA mutant, interferes with Galphaq-mediated signaling pathways. Identification of a YpkA-mediated phosphorylation site in Galphaq sheds light on the contribution of the kinase activity of YpkA to Yersinia pathogenesis.

Nyckelord

Actins/physiology

Bacterial Proteins/metabolism

Cell Line

Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism

GTP-Binding Protein alpha Subunits; Gq-G11/metabolism/*physiology

Humans

Kidney

Phosphorylation

Phosphoserine/metabolism

Protein Binding

Recombinant Fusion Proteins/metabolism

Signal Transduction/*physiology

Stress; Mechanical

Transfection

Yersinia enterocolitica/enzymology/*physiology

Yersinia pestis/enzymology/*physiology

rhoA GTP-Binding Protein/metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)