ADP ribosylation of Arg41 of Rap by ExoS inhibits the ability of Rap to interact with its guanine nucleotide exchange factor, C3G. Biochemistry 2001 Mar 20;40(11):3289-94
Date
03/22/2001Pubmed ID
11258948DOI
10.1021/bi002729qScopus ID
2-s2.0-0035916917 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
ExoS is a bifunctional type III cytotoxin that is secreted by Pseudomonas aeruginosa. The N-terminal domain comprises a RhoGAP activity, while the C-terminal domain comprises a ADP-ribosyltransferase activity. Previous studies showed that ExoS ADP ribosylated Ras at Arg41 which interfered with the ability of Ras to interact with its guanine nucleotide exchange factor. Rap and Ras share considerable primary amino acid homology, including Arg41. In this study, we report that ExoS ADP ribosylates Rap1b at Arg41 and that ADP ribosylation of Arg41 inhibits the ability of C3G to stimulate guanine nucleotide exchange. The mechanism responsible for this inhibition is one in which ADP-ribosylated Rap binds inefficiently to C3G, relative to wild type Rap. This identifies a second member of the Ras GTPase subfamily that can be ADP ribosylated by ExoS and indicates that ExoS can inhibit both Ras and Rap signaling pathways in eukaryotic cells.
Author List
Riese MJ, Wittinghofer A, Barbieri JTAuthor
Joseph T. Barbieri PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ADP Ribose TransferasesAdenosine Diphosphate Ribose
Arginine
Bacterial Toxins
Guanine Nucleotide-Releasing Factor 2
Histidine
Histidine Kinase
Peptide Fragments
Poly(ADP-ribose) Polymerases
Protein Kinases
Pseudomonas aeruginosa
Recombinant Fusion Proteins
Recombinant Proteins
rap GTP-Binding Proteins