Src homology 3 (SH3) domains have been suggested to play an important role in the assembly of the superoxide-forming nicotinamide adenine dinucleotide phosphate (NADPH) oxidase upon activation of phagocytes, which involves the association of membrane-bound and cytosolic components. We studied the translocation of the cytosolic proteins to the plasma membrane in neutrophils of a patient with a point mutation in the gene encoding the light chain of cytochrome b558. This mutation leads to a substitution at residue 156 of a proline into a glutamine in a putative SH3 binding domain of p22-phox (Dinauer, M., E. A. Pierce, R. W. Erickson, T. Muhlebach, H. Messner, R. A. Seger, S. H. Orkin, and J. T. Curnutte. 1991. Proc. Natl. Acad. Sci. 88:11231). In PMA-stimulated neutrophils and in a cell-free translocation assay with neutrophil membranes and cytosol, association of the cytosolic proteins p47-phox and p67-phox with the membrane fraction of the patient's neutrophils was virtually absent. In contrast, when solubilized membranes of the patient's neutrophils were activated with phospholipids in the absence of cytosol (Koshkin, V., and E. Pick. 1993. FEBS [Fed. Eur. Biochem. Soc.] Lett. 327:57), the rate of NADPH-dependent oxygen uptake was observed at a rate similar to that of control membranes. We suggest that the binding of an SH3 domain of p47-phox to p22-phox, and thus activation of the oxidase, does not occur in the neutrophils of this patient, although under artificial conditions, electron flow from NADPH to oxygen in cytochrome b558 is possible.
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December 01 1994
156Pro-->Gln substitution in the light chain of cytochrome b558 of the human NADPH oxidase (p22-phox) leads to defective translocation of the cytosolic proteins p47-phox and p67-phox.
J H Leusen,
J H Leusen
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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B G Bolscher,
B G Bolscher
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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P M Hilarius,
P M Hilarius
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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R S Weening,
R S Weening
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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W Kaulfersch,
W Kaulfersch
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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R A Seger,
R A Seger
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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D Roos,
D Roos
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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A J Verhoeven
A J Verhoeven
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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J H Leusen
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
B G Bolscher
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
P M Hilarius
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
R S Weening
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
W Kaulfersch
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
R A Seger
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
D Roos
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
A J Verhoeven
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 180 (6): 2329–2334.
Citation
J H Leusen, B G Bolscher, P M Hilarius, R S Weening, W Kaulfersch, R A Seger, D Roos, A J Verhoeven; 156Pro-->Gln substitution in the light chain of cytochrome b558 of the human NADPH oxidase (p22-phox) leads to defective translocation of the cytosolic proteins p47-phox and p67-phox.. J Exp Med 1 December 1994; 180 (6): 2329–2334. doi: https://doi.org/10.1084/jem.180.6.2329
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