Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition

Activating mutations of the non-receptor protein tyrosine phosphatase SHP2 can cause cancer. Here the authors present the crystal structure of SHP2E76K, the most frequent cancer-associated SHP2 mutation, which adopts an open-state structure and show that the allosteric inhibitor SHP099 can revert SH...

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Autores principales:	Jonathan R. LaRochelle, Michelle Fodor, Vidyasiri Vemulapalli, Morvarid Mohseni, Ping Wang, Travis Stams, Matthew J. LaMarche, Rajiv Chopra, Michael G. Acker, Stephen C. Blacklow
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/d0fced2ac7bd48d8ba126a11fc5bed5f
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spelling	oai:doaj.org-article:d0fced2ac7bd48d8ba126a11fc5bed5f2021-12-02T15:34:42ZStructural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition10.1038/s41467-018-06823-92041-1723https://doaj.org/article/d0fced2ac7bd48d8ba126a11fc5bed5f2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41467-018-06823-9https://doaj.org/toc/2041-1723Activating mutations of the non-receptor protein tyrosine phosphatase SHP2 can cause cancer. Here the authors present the crystal structure of SHP2E76K, the most frequent cancer-associated SHP2 mutation, which adopts an open-state structure and show that the allosteric inhibitor SHP099 can revert SHP2E76K to its closed, autoinhibited conformation.Jonathan R. LaRochelleMichelle FodorVidyasiri VemulapalliMorvarid MohseniPing WangTravis StamsMatthew J. LaMarcheRajiv ChopraMichael G. AckerStephen C. BlacklowNature PortfolioarticleScienceQENNature Communications, Vol 9, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Jonathan R. LaRochelle Michelle Fodor Vidyasiri Vemulapalli Morvarid Mohseni Ping Wang Travis Stams Matthew J. LaMarche Rajiv Chopra Michael G. Acker Stephen C. Blacklow Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition
description	Activating mutations of the non-receptor protein tyrosine phosphatase SHP2 can cause cancer. Here the authors present the crystal structure of SHP2E76K, the most frequent cancer-associated SHP2 mutation, which adopts an open-state structure and show that the allosteric inhibitor SHP099 can revert SHP2E76K to its closed, autoinhibited conformation.
format	article
author	Jonathan R. LaRochelle Michelle Fodor Vidyasiri Vemulapalli Morvarid Mohseni Ping Wang Travis Stams Matthew J. LaMarche Rajiv Chopra Michael G. Acker Stephen C. Blacklow
author_facet	Jonathan R. LaRochelle Michelle Fodor Vidyasiri Vemulapalli Morvarid Mohseni Ping Wang Travis Stams Matthew J. LaMarche Rajiv Chopra Michael G. Acker Stephen C. Blacklow
author_sort	Jonathan R. LaRochelle
title	Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition
title_short	Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition
title_full	Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition
title_fullStr	Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition
title_full_unstemmed	Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition
title_sort	structural reorganization of shp2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d0fced2ac7bd48d8ba126a11fc5bed5f
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Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition

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