Vav proteins control MyD88-dependent oxidative burst
Abstract
The importance of reactive oxygen intermediate (ROI) production in antimicrobial responses is demonstrated in human patients who suffer from chronic granulomatous disease (CGD) due to defective NADPH oxidase function. Exactly how bacterial products activating Toll-like receptors (TLRs) induce oxidative burst is unknown. Here, we identify the Vav family of Rho guanine nucleotide exchange factors (GEFs) as critical mediators of LPS-induced MyD88-dependent activation of Rac2, NADPH oxidase, and ROI production using mice deficient in Vav1, Vav2, and Vav3. Vav proteins are also required for p38 MAPK activation and for normal regulation of proinflammatory cytokine production, but not for other MyD88-controlled effector pathways such as those involving JNK, COX2, or iNOS and the production of reactive nitrogen intermediates (RNIs). Thus, our data indicate that Vav specifically transduces a subset of signals emanating from MyD88.
Document Type
Article
DOI
https://doi.org/10.1182/blood-2006-07-033662
Keywords
immunobiology and immunotherapy, signal transduction
Publication Date
2006
Recommended Citation
Miletic, Ana V., Daniel B. Graham, Vivianne Montgrain, Keiko Fujikawa, Tracie Kloeppel, Karry Brim, Brian Weaver, Robert Schreiber, Ramnik Xavier, and Wojciech Swat. "Vav proteins control MyD88-dependent oxidative burst." Blood 109, no. 8 (2007): 3360-3368.
Journal Title
Blood
