Phagocyte NADPH oxidase p67-phox possesses a novel carboxylterminal binding site for the GTPases Rac2 and Cdc42

Biochemical and Biophysical Research Communications
S L FarisM E Kleinberg

Abstract

Rac GTPases regulate activation of the phagocyte NADPH oxidase, a multi-component enzyme complex that produces superoxide in response to host infection. GTP-bound Rac binds to the cytosol protein p67-phox enabling it to participate in oxidase assembly. Details of this interaction are poorly understood. Previous studies showed that Rac/p67-phox binding is GTP-dependent and that several Rac1 mutants lost the ability to activate the oxidase even though they still bound p67-phox. Using two hybrid and blot overlay binding methods, we identified a novel binding site in the p67-phox C-terminus that binds Rac1, Rac2, and Cdc42, a related GTPase which does not activate the oxidase. Binding was independent of the GDP/GTP state. We also showed that GTP-Cdc42 binds p67-phox N-terminus similar to GTP-Rac. Therefore, Rac binding to p67-phox is not synonymous with NADPH oxidase activation, and Rac probably participates in other steps of oxidase activation in addition to binding p67-phox.

References

Dec 8, 1995·The Journal of Biological Chemistry·P D BurbeloA Hall
Aug 25, 1995·The Journal of Biological Chemistry·C H KwongT L Leto
Sep 1, 1995·Journal of Leukocyte Biology·M T Quinn
Nov 1, 1993·European Journal of Haematology·G M Bokoch
Dec 26, 1995·Biochemistry·J HuangM E Kleinberg
Jan 5, 1996·The Journal of Biological Chemistry·O DorseuilG Gacon
Oct 1, 1996·The Journal of Experimental Medicine·J H LeusenD Roos
Feb 3, 1998·Molecular and Cellular Biology·K F ToliasC L Carpenter

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Citations

Feb 5, 1999·The Biochemical Journal·L V ForbesA W Segal
Apr 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·D R AmbrusoD Roos
Jul 9, 2004·Journal of Leukocyte Biology·Mark T Quinn, Katherine A Gauss
Jul 18, 2001·American Journal of Physiology. Renal Physiology·T KuncewiczB C Kone
Sep 16, 1999·Biochemical and Biophysical Research Communications·L A RinckelM E Kleinberg
Jul 30, 1999·Biochimica Et Biophysica Acta·L C McPhailS Sergeant
Nov 24, 1999·Biochimica Et Biophysica Acta·H NishiharaM Matsuda

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