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Article

Phosphatase SHP2 pathogenic mutations enhance activity by altering conformational sampling.

Proceedings of the National Academy of Sciences of the United States of America - 20 Jan 2026

Glaser Andrew W, Pádua Ricardo A P, Ojoawo Adedolapo M, Sullivan Camille, Kern Dorothee

Abstract excerpt

SH2 domains are critical mediators of cellular signaling, although the molecular mechanisms by which they bind their phosphopeptide ligands remain incompletely understood. We investigate the atomic mechanisms underlying both healthy regulation and dysregulation of the human protein tyrosine phosphatase SHP2, a key regulator of cellular signaling. While most pathogenic mutations cluster near the PTP/N-SH2...

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Identifiers

PMID: 41528873
DOI: 10.1073/pnas.2513851123
PMCID: PMC12818432

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