Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 15 September 2009
Vol. 2, Issue 88, p. ra54
[DOI: 10.1126/scisignal.2000370]

RESEARCH ARTICLES

Novel p47phox-Related Organizers Regulate Localized NADPH Oxidase 1 (Nox1) Activity

Davide Gianni1,2, Begoña Diaz3, Nicolas Taulet1,2, Bruce Fowler1,2, Sara A. Courtneidge3*, and Gary M. Bokoch1,2*

1 Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
3 Tumor Microenvironment Program, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA.

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 functional members 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- and Nox-dependent fashion. We propose that Tks organizers represent previously unrecognized members of an organizer superfamily that link Nox to localized ROS formation.

* To whom correspondence should be addressed. E-mail: bokoch{at}scripps.edu (G.M.B.) and courtneidge{at}burnham.org (S.A.C.)

Citation: D. Gianni, B. Diaz, N. Taulet, B. Fowler, S. A. Courtneidge, G. M. Bokoch, Novel p47phox-Related Organizers Regulate Localized NADPH Oxidase 1 (Nox1) Activity. Sci. Signal. 2, ra54 (2009).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Frank-ter Haar Syndrome Protein Tks4 Regulates Epidermal Growth Factor-dependent Cell Migration.
G. Bogel, A. Gujdar, M. Geiszt, A. Lanyi, A. Fekete, S. Sipeki, J. Downward, and L. Buday (2012)
J. Biol. Chem. 287, 31321-31329
   Abstract »    Full Text »    PDF »
Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell-cell fusion.
T. Oikawa, M. Oyama, H. Kozuka-Hata, S. Uehara, N. Udagawa, H. Saya, and K. Matsuo (2012)
J. Cell Biol. 197, 553-568
   Abstract »    Full Text »    PDF »
c-Src-Mediated Phosphorylation of NoxA1 and Tks4 Induces the Reactive Oxygen Species (ROS)-Dependent Formation of Functional Invadopodia in Human Colon Cancer Cells.
D. Gianni, N. Taulet, C. DerMardirossian, and G. M. Bokoch (2010)
Mol. Biol. Cell 21, 4287-4298
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 5 January 2010.
M. B. Yaffe and A. M. VanHook (2010)
Science Signaling 3, pc1
   Abstract »    Full Text »
Regulation of Cancer Invasion by Reactive Oxygen Species and Tks Family Scaffold Proteins.
A. M. Weaver (2009)
Science Signaling 2, pe56
   Abstract »    Full Text »    PDF »
Tks5-Dependent, Nox-Mediated Generation of Reactive Oxygen Species Is Necessary for Invadopodia Formation.
B. Diaz, G. Shani, I. Pass, D. Anderson, M. Quintavalle, and S. A. Courtneidge (2009)
Science Signaling 2, ra53
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882