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

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

doi:10.1126/scisignal.2000370

Novel p47^phox-related organizers regulate localized NADPH oxidase 1 (Nox1) activity

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

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

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 p47^phox-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 language	English (US)
Pages (from-to)	ra54
Journal	Science signaling
Volume	2
Issue number	88
DOIs	https://doi.org/10.1126/scisignal.2000370
State	Published - Sep 15 2009
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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title = "Novel p47phox-related organizers regulate localized NADPH oxidase 1 (Nox1) activity",

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.",

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AU - Gianni, Davide

AU - Diaz, Begoña

AU - Taulet, Nicolas

AU - Fowler, Bruce

AU - Courtneidge, Sara A.

AU - Bokoch, Gary M.

PY - 2009/9/15

Y1 - 2009/9/15

N2 - 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.

AB - 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.

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Novel p47^phox-related organizers regulate localized NADPH oxidase 1 (Nox1) activity

Abstract

ASJC Scopus subject areas

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