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Author John D Lapek

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Reversible lysine-targeted probes reveal residence time-based kinase selectivity.

Tangpo Yang, Adolfo Cuesta, Xiaobo Wan, Gregory B Craven, Brad Hirakawa, Penney Khamphavong, Jeffrey R May, John C Kath, John D Lapek, Sherry Niessen, Alma L Burlingame, Jordan D Carelli, Jack Taunton,

The expansion of the target landscape of covalent inhibitors requires the engagement of nucleophiles beyond cysteine. Although the conserved catalytic lysine in protein kinases is an attractive candidate for a covalent approach, selectivity remains an obvious challenge. Moreover, few covalent inhibitors have been shown to engage the kinase catalytic lysine ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2022, :]

Cited: 0 times

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Phosphoproteomic analysis of protease-activated receptor-1 biased signaling reveals unique modulators of endothelial barrier function.

Ying Lin, Jacob M Wozniak, Neil J Grimsey, Sravan Girada, Anand Patwardhan, Olivia Molinar-Inglis, Thomas H Smith, John D Lapek, David J Gonzalez, JoAnn Trejo,

Thrombin, a procoagulant protease, cleaves and activates protease-activated receptor-1 (PAR1) to promote inflammatory responses and endothelial dysfunction. In contrast, activated protein C (APC), an anticoagulant protease, activates PAR1 through a distinct cleavage site and promotes anti-inflammatory responses, prosurvival, and endothelial barrier stabilization. The distinct tethered ligands formed through cleavage of ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, 117(9):5039-5048]

Cited: 8 times

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