Inhibition of MAPK signaling pathways by VopA from Vibrio parahaemolyticus.
During infection, bacterial pathogens utilize a type III secretion system to inject effectors into the cytoplasm of a target cell where they disrupt the defense system of the host cell. Vibrio parahaemolyticus, a causative agent of gastroenteritis endemic in Southeast Asia, has a type III secretion system that encodes a novel member of the YopJ-like protein effector family, VopA (Vibrio outer protein A). Our studies revealed that Vibrio VopA encodes an evolutionarily conserved activity that is extremely potent and requires an intact catalytic site to abrogate signaling pathways in a manner distinct from that of other YopJ-like effectors. We observed that VopA efficiently inhibits the MAPK signaling pathways but not the NFkappaB pathway in mammalian cells. When expressed in yeast, VopA induces a growth arrest phenotype and also blocks yeast MAPK signaling pathways. Our observations provide insight into the immense diversity of targets utilized by YopJ-like effectors to manipulate eukaryotic signaling machineries that are important for the response and survival of the host cell during infection and/or symbiosis.
Department of Molecular Biology, University of Texas Southwestern Medical School, Dallas, Texas 75390-9148, USA.
Jennifer E
JE
Trosky
Sohini
S
Mukherjee
Dara L
DL
Burdette
Margaret
M
Roberts
Linda
L
McCarter
Richard M
RM
Siegel
Kim
K
Orth
D000595:Amino Acid Sequence; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014736:Vibrio parahaemolyticus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity
D001426:Bacterial Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; C109227:YopP protein, Yersinia