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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3962-3969. Prepublished online as a Blood First Edition Paper on August 11, 2005; DOI 10.1182/blood-2005-03-0859. This Article Full Text (PDF) All Versions of this Article: 2005-03-0859v1 106/12/3962    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Martyn, K. D Articles by Knaus, U. G Search for Related Content PubMed PubMed Citation Articles by Martyn, K. D Articles by Knaus, U. G Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 2, 2005 Accepted July 17, 2005 P-21 activated kinase (Pak) regulates NADPH oxidase activation in human neutrophils Kendra D Martyn, Moon-Ju Kim, Mark T Quinn, Mary C Dinauer, and Ulla G Knaus* Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT, USA Department of Pediatrics,Hematology/Oncology and Medical and Molecular Genetics, The Herman B Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children, Indiana University Medical Center, Indianapolis, IN, USA * Corresponding author; email: uknaus{at}scripps.edu. The phagocyte NADPH oxidase plays an instrumental role in host defense and contributes to microbicial killing by releasing highly reactive oxygen species. This multi-component enzyme is composed of membrane and cytosolic components that assemble in the plasma membrane or phagolysosome. While the GTPase Rac2 has been shown to be a critical regulator of NADPH oxidase activity and assembly, the role of its effector, p21-activated kinase (Pak), in oxidase function has not been well-defined. Using Tat-mediated protein transduction of Pak inhibitory domain, we show here that Pak activity is indeed required for efficient superoxide generation in intact neutrophils. Furthermore, we show Pak translocates to the plasma membrane upon fMLF stimulation and co-localizes with translocated p47phox and with p22phox, a subunit of flavocytochrome b558. Although activated Pak phosphorylated several essential serine residues in the C-terminus of p47phox direct binding to p47phox was not observed. In contrast, active Pak bound directly to p22phox, suggesting flavocytochrome b was the oxidase-associated membrane target of this kinase and this association may facilitate further phosphorylation of p47phox in the assembling NADPH oxidase complex. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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