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Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity.

ABSTRACT: Protein sulfenylation is a post-translational modification of emerging importance in higher eukaryotes. However, investigation of its diverse roles remains challenging, particularly within a native cellular environment. Herein we report the development and application of DYn-2, a new chemoselective probe for detecting sulfenylated proteins in human cells. These studies show that epidermal growth factor receptor-mediated signaling results in H(2)O(2) production and oxidation of downstream proteins. In addition, we demonstrate that DYn-2 has the ability to detect differences in sulfenylation rates within the cell, which are associated with differences in target protein localization. We also show that the direct modification of epidermal growth factor receptor by H(2)O(2) at a critical active site cysteine (Cys797) enhances its tyrosine kinase activity. Collectively, our findings reveal sulfenylation as a global signaling mechanism that is akin to phosphorylation and has regulatory implications for other receptor tyrosine kinases and irreversible inhibitors that target oxidant-sensitive cysteines in proteins.

SUBMITTER: Paulsen CE

PROVIDER: S-EPMC3528018 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity.

Paulsen Candice E CE Truong Thu H TH Garcia Francisco J FJ Homann Arne A Gupta Vinayak V Leonard Stephen E SE Carroll Kate S KS

Nature chemical biology 20111211 1

Protein sulfenylation is a post-translational modification of emerging importance in higher eukaryotes. However, investigation of its diverse roles remains challenging, particularly within a native cellular environment. Herein we report the development and application of DYn-2, a new chemoselective probe for detecting sulfenylated proteins in human cells. These studies show that epidermal growth factor receptor-mediated signaling results in H(2)O(2) production and oxidation of downstream protein ...[more]

PMID: 22158416

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Dataset Information

Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity.

Publications

Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity.

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