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The eukaryotic host factor that activates exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family. Proc Natl Acad Sci U S A 1993 Mar 15;90(6):2320-4 PMID: 8460141 PMCID: PMC46078

Pubmed ID

8460141

Abstract

Exoenzyme S (ExoS), which has been implicated as a virulence factor of Pseudomonas aeruginosa, catalyzes transfer of the ADP-ribose moiety of NAD+ to many eukaryotic cellular proteins. Its preferred substrates include Ras and several other 21- to 25-kDa GTP-binding proteins. ExoS absolutely requires a ubiquitous eukaryotic protein factor, termed FAS (factor activating ExoS), for enzymatic activity. Here we describe the cloning and expression of a gene encoding FAS from a bovine brain cDNA library and demonstrate that purified recombinant FAS produced in Escherichia coli activates ExoS in a defined cell-free system. The deduced amino acid sequence of FAS shows that the protein (245 residues, calculated molecular mass 27,743 Da) belongs to a highly conserved, widely distributed eukaryotic protein family, collectively designated as 14-3-3 proteins. Various functions have been reported for members of the 14-3-3 family, including phospholipase A2 activity and regulation of tyrosine hydroxylase, tryptophan hydroxylase, and, possibly, protein kinase C activities. Identification of FAS as a 14-3-3 protein establishes an additional function for this family of proteins--the activation of an exogenous ADP-ribosyltransferase. Elucidation of the precise role of FAS in activating ExoS will contribute to understanding the molecular mechanisms by which P. aeruginosa causes disease.

Author List

Fu H, Coburn J, Collier RJ

Author

Jenifer Coburn PhD Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-0027461546   198 Citations

MESH terms used to index this publication - Major topics in bold

14-3-3 Proteins
ADP Ribose Transferases
Amino Acid Sequence
Animals
Bacterial Toxins
Base Sequence
Brain
Cattle
Enzyme Activation
Gene Library
Genetic Vectors
Humans
Molecular Sequence Data
Molecular Weight
Multigene Family
Nerve Tissue Proteins
Oligodeoxyribonucleotides
Phylogeny
Poly(ADP-ribose) Polymerases
Polymerase Chain Reaction
Pseudomonas aeruginosa
Restriction Mapping
Sequence Homology, Amino Acid
Tyrosine 3-Monooxygenase
jenkins-FCD Prod-300 626508253d14e4184314fb9f66322a03a5906796