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.
Navarro
Lorena
L
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Koller
Antonius
A
Nordfelth
Roland
R
Wolf-Watz
Hans
H
Taylor
Susan
S
Dixon
Jack E
JE
D000199:Actins / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007668:Kidney; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D014162:Transfection; D015008:Yersinia enterocolitica / Q000201:enzymology / Q000502:physiology*; D015010:Yersinia pestis / Q000201:enzymology / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D001426:Bacterial Proteins; D011993:Recombinant Fusion Proteins; D010768:Phosphoserine; D017868:Cyclic AMP-Dependent Protein Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020742:rhoA GTP-Binding Protein