Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations

Zhi Hong Yu, Jie Xu, Chad D. Walls, Lan Chen, Sheng Zhang, Ruoyu Zhang, Li Wu, Lina Wang, Sijiu Liu, Zhong Yin Zhang

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Background: The mechanism by which SHP2 mutations cause LEOPARD syndrome is poorly understood. Results: LEOPARD syndrome mutations impair SHP2 activity but increase its propensity for an open and active conformation. Conclusion: LEOPARD syndrome SHP2 mutants bind preferentially to upstream activators to prolong substrate turnover, thus engendering gain-of-function phenotypes. Significance: The study provides a framework for understanding how individual SHP2 mutations cause diseases.

Original languageEnglish (US)
Pages (from-to)10472-10482
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number15
DOIs
StatePublished - Apr 12 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yu, Z. H., Xu, J., Walls, C. D., Chen, L., Zhang, S., Zhang, R., Wu, L., Wang, L., Liu, S., & Zhang, Z. Y. (2013). Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations. Journal of Biological Chemistry, 288(15), 10472-10482. https://doi.org/10.1074/jbc.M113.450023