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

41 Citations (Scopus)

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

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LEOPARD Syndrome
Conformations
Mutation
Substrates
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations. / Yu, Zhi Hong; Xu, Jie; Walls, Chad D.; Chen, Lan; Zhang, Sheng; Zhang, Ruoyu; Wu, Li; Wang, Lina; Liu, Sijiu; Zhang, Zhong-Yin.

In: Journal of Biological Chemistry, Vol. 288, No. 15, 12.04.2013, p. 10472-10482.

Research output: Contribution to journalArticle

Yu, ZH, Xu, J, Walls, CD, 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, vol. 288, no. 15, pp. 10472-10482. https://doi.org/10.1074/jbc.M113.450023
Yu, Zhi Hong ; Xu, Jie ; Walls, Chad D. ; Chen, Lan ; Zhang, Sheng ; Zhang, Ruoyu ; Wu, Li ; Wang, Lina ; Liu, Sijiu ; Zhang, Zhong-Yin. / Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 15. pp. 10472-10482.
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