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J Am Chem Soc. 2012 Mar 7;134(9):3976-8. doi: 10.1021/ja211089v. Epub 2012 Feb 22.

Rewiring kinase specificity with a synthetic adaptor protein.

Author information

1
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.

Abstract

Signaling cascades are managed in time and space by interactions between and among proteins. These interactions are often aided by adaptor proteins, which guide enzyme-substrate pairs into proximity. Miniature proteins are a class of small, well-folded protein domains possessing engineered binding properties. Here we made use of two miniature proteins with complementary binding properties to create a synthetic adaptor protein that effectively redirects a ubiquitous signaling event: tyrosine phosphorylation. We report that miniature-protein-based adaptor 3 uses templated catalysis to redirect the Src family kinase Hck to phosphorylate hDM2, a negative regulator of the p53 tumor suppressor and a poor Hck substrate. Phosphorylation occurs with multiple turnover and at a single site targeted by c-Abl kinase in the cell.

PMID:
22352870
PMCID:
PMC3328303
DOI:
10.1021/ja211089v
[Indexed for MEDLINE]
Free PMC Article

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