A 68-kDa Kinase and NADPH Oxidase Component p67  Are Targets for Cdc42Hs and Rac1 in Neutrophils

Prigmore, Elena; Ahmed, Sohail; Best, A.; Kozma, Robert; Manser, Edward; Segal, Anthony W.; Lim, Louis

doi:10.1074/jbc.270.18.10717

Cited by 78 publications

(71 citation statements)

References 21 publications

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“…Expression of constitutively active Rac1 derivatives also stimulated p47 phox translocation to the plasma membrane, even in the absence of p67 phox expression, although Rac-GTP does not directly bind to p47 phox (23,54). In neutrophils, current evidence indicates that p47 phox membrane translocation requires phosphorylation of multiple serine residues, including serines 303, 304, and 328, to expose an SH-3 domain necessary for p47…”

Section: Activation Of Endogenous Rac1 By Transgenic Expression Of Ramentioning

confidence: 87%

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Rac Activation Induces NADPH Oxidase Activity in Transgenic COS Cells, and the Level of Superoxide Production Is Exchange Factor-dependent

Price¹,

Atkinson²,

Knaus³

et al. 2002

Journal of Biological Chemistry

110

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. Rac effector domain point substitutions (A27K, G30S, D38A, Y40C), which can selectively eliminate interaction with different effector proteins, impaired Rac1V12-induced superoxide production. Activation of endogenous Rac1 by expression of constitutively active Rac-guanine nucleotide exchange factor (GEF) derivatives was sufficient to induce high level NADPH oxidase activity in COS phox cells. The constitutively active form of the hematopoieticspecific GEF, Vav1, was the most effective at activating superoxide production, despite detection of higher levels of Rac1-GTP upon expression of constitutively active Vav2 or Tiam1 derivatives. These data suggest that Rac can play a dual role in NADPH oxidase activation, both by directly participating in the oxidase complex and by activating signaling events leading to oxidase assembly, and that Vav1 may be the physiologically relevant GEF responsible for activating this Racregulated complex.

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Section: Activation Of Endogenous Rac1 By Transgenic Expression Of Ramentioning

confidence: 87%

“…phox (23,54). Rac1L61 and Rac1V12/S30 also induced p47 phox membrane translocation in COS-91,22,47 cells (data not shown).…”

Section: Expression Of Activated Rac Is Sufficient Tomentioning

confidence: 94%

Rac Activation Induces NADPH Oxidase Activity in Transgenic COS Cells, and the Level of Superoxide Production Is Exchange Factor-dependent

Price¹,

Atkinson²,

Knaus³

et al. 2002

Journal of Biological Chemistry

110

View full text Add to dashboard Cite

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“…A direct interaction between p67 phox and Rac has been reported by several laboratories using p67 phox affinity chromatography (27), binding to nitrocellulose-blotted protein (43,49), and the yeast two-hybrid method (50). In these studies, changes in residues 26 -45 and 143-175 inhibited binding to p67 phox , implying that the interaction occurs directly with the Ras homologous effector region and an effector region C-terminal to the GTP binding domain.…”

Section: Fig 8 Concentration Dependence For P47mentioning

confidence: 92%

Rac “Insert Region” Is a Novel Effector Region That Is Implicated in the Activation of NADPH Oxidase, but Not PAK65

Freeman

Abo²,

Lambeth

1996

Journal of Biological Chemistry

139

133

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The small GTPase Rac assembles with the cytosolic p47 phox and p67 phox and the membrane-associated flavocytochrome b 558 to form the multicomponent respiratory burst oxidase. Mutation of amino acids in a region of Rac (residues 26 -45), homologous to an effector region in Ras, was previously shown to interfere with Rac binding to the oxidase. Herein we have elucidated an additional region in Rac involved in regulating oxidase activity. Rho family small GTPases contain a 12-amino acid "insert" region (residues 124 -135) that is not present in Ras. Point mutations in and deletion of this region were constructed and used for in vitro studies of the activation of PAK65 and NADPH oxidase. During the respiratory burst, neutrophils and other phagocytic cells reduce molecular oxygen to generate superoxide anion, with subsequent production of secondary products such as hydrogen peroxide and hydroxyl radical, all of which participate in microbial killing. The enzyme that initiates the respiratory burst, the NADPH oxidase, is a multicomponent enzyme that utilizes reducing equivalents from NADPH to reduce oxygen to superoxide (reviewed in Ref.

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“…Two potential targets for rac1 have been discovered: p67-phox and the serine kinase p68-pak, related to the brain p65-pak (144,145). The GTP-bound rac activates p68-pak, which in turn phosphorylates p47-phox on 328 Ser (146).…”

Section: Role Of Rac and Rap1a In Activating The Oxidasementioning

confidence: 99%

Interactions between the components of the human nadph oxidase: intrigues in the phox family

Leusen

Verhoeven

Roos

1996

Journal of Laboratory and Clinical Medicine

113

108

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A 68-kDa Kinase and NADPH Oxidase Component p67 Are Targets for Cdc42Hs and Rac1 in Neutrophils

Cited by 78 publications

References 21 publications

Rac Activation Induces NADPH Oxidase Activity in Transgenic COS Cells, and the Level of Superoxide Production Is Exchange Factor-dependent

Rac Activation Induces NADPH Oxidase Activity in Transgenic COS Cells, and the Level of Superoxide Production Is Exchange Factor-dependent

Rac “Insert Region” Is a Novel Effector Region That Is Implicated in the Activation of NADPH Oxidase, but Not PAK65

Interactions between the components of the human nadph oxidase: intrigues in the phox family

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