p47phox

p47^phox

^{updated
17/5/02}

Neutrophils are activated by a number of chemoattractants and cytokines which direct the cells to crawl up the gradient in order to accumulate at site of infection or inflammation. FMet.Leu.Phe. is the best studied chemoattractant and at modest concntrations (around 1x10^-8M) it stimulates locomotion, however at higher concentrations this peptide stimulates the production of 0₂^-, a highly reactive species that is generally believed to be responsible for bacterial killing in the phagosome. The complex of enzymes that produces this superoxide radical include p47^PHOX, p67^PHOX, NADPH oxidase, membrane bound cytochrome b₅₅₈II. The details of the complex are not known fully but p67^PHOX binds cytochrome b₅₅₈II directly (Dang et al, 2002), and p47^PHOX binds actin (Tamara et al, 2000). The significance of this later connection are presently unknown but possibly connected with the fact that actin depolymerization seems to be required for NADPH oxidase activation (Al-Mohanna et al, 1990), and that cofilin may be involved (Suzuki et al, 1995).

References:-

Ago, T., Kuribayashi, F., Hiroaki, H., Takeya, R., Ito, T., Kohda, D. & Sumimoto, H. (2003) Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation. PNAS. 100, 4474-4479.

Al-Mohanna, F. A. & Hallett, M. B. (1990) "Clamping" actin in polymerized formin electropermeabilized neutrophils inhibits oxidase activation., Biochem.Biophys.Res.Commun. 169, 1222-1228.

Dang, P. M.-C., Cross, A. R., Quinn, M. T. & Baboir, B. M. (2002) Assembly of the neutrophil respiratory burst oxidase: a direct interaction between p67^PHOXand cytochrome b_{558^{II., PNAS. 99, 4262-4265.}}

El Benna, J., Dang, P. M.-c., Andrieu, V., Vergnaud, S., Dewas, C., Cachia, O., Fay, M., Morel, F., Chollet-Martin, S., Hakim, J. & Gougerot-Pocidalo, M.-A. (1999) P40^{phox
associates with the neutrophil triton X-100-insoluble cytoskeleton fraction and
PMA-activated membrane skeleton: a comparative study with P67phox
and P47phox. J.Leuk.Biol. 66,
1014-1020.}

Howard, T., Li, Y., Torres, M., Guerrero, A. & Coates, T. (1994) The 47-kD protein increased in neutrophil actin dysfunction with 47- and 89-kD protein abnormalitites is lymphocyte-specific protein, Blood. 83, 231-241.

Suzuki, K., Yamaguchi, T., Oshizawa, T., Yamamoto, Y., Nishimaki-Mogami, T., Hayakawa, T. & Takahashi, A. (1995) Okadaic acid induces both augmentation and inhibition of opsonized zymosan-stimulated superoxide production by differentiated HL-60 cells - possible involvement of dephosphorylation of a cytosolic 21k protein in respiratory burst Biochim. Biophys. Acta. 1266, 261-267.

Tamura, M., Kai, T., Tsunawaki, S., Lambeth, J.D. & Kameda, K. (2000). "Direct interaction of actin with p47^phox of neutrophil NADPH oxidase." B.B.R.C. 276(3), 1186-1190.