Novel p47phox-related organizers regulate localized NADPH oxidase 1 (Nox1) activity

Davide Gianni, Begoña Diaz, Nicolas Taulet, Bruce Fowler, Sara Courtneidge, Gary M. Bokoch

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The mechanisms that determine localized formation of reactive oxygen species (ROS) through NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox) family members in nonphagocytic cells are unknown. We show that the c-Src substrate proteins Tks4 (tyrosine kinase substrate with four SH3 domains) and Tks5 are functionalmembers of a p47phox-related organizer superfamily. Tks proteins selectively support Nox1 and Nox3 (and not Nox2 and Nox4) activity in reconstituted cellular systems and interact with the NoxA1 activator protein through an Src homology 3 domain-mediated interaction. Endogenous Tks4 is required for Rac guanosine triphosphatase- and Nox1-dependent ROS production by DLD1 colon cancer cells. Our results are consistent with the Tks-mediated recruitment of Nox1 to invadopodia that form in DLD1 cells in a Tks- andNox-dependent fashion.Wepropose that Tks organizers represent previously unrecognized members of an organizer superfamily that link Nox to localized ROS formation.

Original languageEnglish (US)
JournalScience Signaling
Volume2
Issue number88
DOIs
StatePublished - Sep 15 2009
Externally publishedYes

Fingerprint

NADP
Reactive Oxygen Species
Oxidoreductases
src Homology Domains
Proteins
Guanosine
Substrates
Protein-Tyrosine Kinases
Colonic Neoplasms
Cells
NADPH oxidase 1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Novel p47phox-related organizers regulate localized NADPH oxidase 1 (Nox1) activity. / Gianni, Davide; Diaz, Begoña; Taulet, Nicolas; Fowler, Bruce; Courtneidge, Sara; Bokoch, Gary M.

In: Science Signaling, Vol. 2, No. 88, 15.09.2009.

Research output: Contribution to journalArticle

Gianni, Davide ; Diaz, Begoña ; Taulet, Nicolas ; Fowler, Bruce ; Courtneidge, Sara ; Bokoch, Gary M. / Novel p47phox-related organizers regulate localized NADPH oxidase 1 (Nox1) activity. In: Science Signaling. 2009 ; Vol. 2, No. 88.
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