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Science 301 (5633): 657-661

Copyright © 2003 by the American Association for the Advancement of Science

Screening for Nitric Oxide-Dependent Protein-Protein Interactions

Akio Matsumoto, Karrie E. Comatas, Limin Liu, Jonathan S. Stamler*

Abstract: Because nitric oxide (NO) may be a ubiquitous regulator of cellular signaling, we have modified the yeast two-hybrid system to explore the possibility of NO-dependent protein-protein interactions.We screened for binding partners of procaspase-3, a protein implicated in apoptotic signaling pathways, and identified multiple NO-dependent interactions.Two such interactions, with acid sphingomyelinase and NO synthase, were shown to occur in mammalian cells dependent on endogenous NO.Nitrosylation may thus provide a broad-based mechanism for regulating interactions between proteins.If so, systematic proteomic analyses in which redox state and NO bioavailability are carefully controlled will reveal a large array of novel interactions.

Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

* To whom correspondence should be addressed. E-mail: STAML001{at}

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