Rewiring kinase specificity with a synthetic adaptor protein.

Journal of the American Chemical Society
Elissa M Hobert, Alanna Schepartz

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.

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Citations

Dec 18, 2013·Bioconjugate Chemistry·Jianpeng WangJiang Xia
Feb 19, 2014·Journal of the American Chemical Society·Karla Camacho-SotoIndraneel Ghosh
Oct 30, 2015·Future Medicinal Chemistry·Ronny Peri-NaorDavid Margulies
Mar 18, 2017·ACS Chemical Biology·Catherine ChenBenjamin E Turk
Nov 20, 2014·Journal of the American Chemical Society·Karla Camacho-SotoIndraneel Ghosh
Nov 20, 2014·Organic & Biomolecular Chemistry·Anna BarnardAndrew J Wilson
Apr 26, 2020·Angewandte Chemie·Lenne J M LemmensLuc Brunsveld
Jul 19, 2012·Angewandte Chemie·Christoph Meyer, Maja Köhn
Aug 1, 2013·Israel Journal of Chemistry·Elissa M HobertAlanna Schepartz
Nov 6, 2018·Chemical Science·Jordan M FletcherDerek N Woolfson
Aug 14, 2020·Journal of the American Chemical Society·Sachini U SiriwardenaAmit Choudhary
Jul 17, 2021·Cell Chemical Biology·Ashley E ModellAmit Choudhary
May 7, 2020·Bioconjugate Chemistry·Lenne J M LemmensLuc Brunsveld

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