期刊
BLOOD
卷 106, 期 12, 页码 3962-3969出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-03-0859
关键词
-
类别
资金
- NCRR NIH HHS [M01 RR00833] Funding Source: Medline
- NHLBI NIH HHS [HL45635] Funding Source: Medline
- NIAID NIH HHS [AI35947] Funding Source: Medline
- NIAMS NIH HHS [AR42426] Funding Source: Medline
- NIDDK NIH HHS [T32 DK07022] Funding Source: Medline
The phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays an instrumental role in host defense and contributes to microbicial killing by releasing highly reactive oxygen species. This multicomponent enzyme is composed of membrane and cytosolic components that assemble in the plasma membrane or phagolysosome. While the guanosine S'-triphosphatase (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 HIV-1 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 that Pak translocates to the plasma membrane upon N-formyl-methionyl-leucyl-phenylalanine (fMLF) stimulation and colocalizes with translocated P47(phox) and with p22(phox), a subunit of flavocytochrome b(558). Although activated Pak phosphorylated several essential serine residues in the C-terminus of P47phox, direct binding to p47(phox) was not observed. In contrast, active Pak bound directly to p22(phox) suggesting flavocytochrome b was the oxidase-associated membrane target of this kinase and this association may facilitate further phosphorylation of P47(phox) in the assembling NADPH oxidase complex.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据