Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli

Handle URI:
http://hdl.handle.net/10754/562754
Title:
Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli
Authors:
Suen, KinMan; Lin, Chichuan; George, Roger R.; Melo, Fernando A.; Biggs, Eleanor R.; Ahmed, Zamal; Drake, Melanie N.; Arur, Swathi; Arold, Stefan T. ( 0000-0001-5278-0668 ) ; Ladbury, John E S D
Abstract:
Control mechanisms that prevent aberrant signaling are necessary to maintain cellular homeostasis. We describe a new mechanism by which the adaptor protein Shc directly binds the MAP kinase Erk, thus preventing its activation in the absence of extracellular stimuli. The Shc-Erk complex restricts Erk nuclear translocation, restraining Erk-dependent transcription of genes, including those responsible for oncogenic growth. The complex forms through unique binding sites on both the Shc PTB domain and the N-terminal lobe of Erk. Upon receptor tyrosine kinase stimulation, a conformational change within Shc - induced through interaction with the phosphorylated receptor - releases Erk, allowing it to fulfill its role in signaling. Thus, in addition to its established role in promoting MAP kinase signaling in stimulated cells, Shc negatively regulates Erk activation in the absence of growth factors and thus could be considered a tumor suppressor in human cells. © 2013 Nature America, Inc. All rights reserved.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program; Computational Bioscience Research Center (CBRC); Structural Biology and Engineering
Publisher:
Nature Publishing Group
Journal:
Nature Structural and Molecular Biology
Issue Date:
1-May-2013
DOI:
10.1038/nsmb2557
PubMed ID:
23584453
Type:
Article
ISSN:
15459993
Appears in Collections:
Articles; Bioscience Program; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorSuen, KinManen
dc.contributor.authorLin, Chichuanen
dc.contributor.authorGeorge, Roger R.en
dc.contributor.authorMelo, Fernando A.en
dc.contributor.authorBiggs, Eleanor R.en
dc.contributor.authorAhmed, Zamalen
dc.contributor.authorDrake, Melanie N.en
dc.contributor.authorArur, Swathien
dc.contributor.authorArold, Stefan T.en
dc.contributor.authorLadbury, John E S Den
dc.date.accessioned2015-08-03T11:04:27Zen
dc.date.available2015-08-03T11:04:27Zen
dc.date.issued2013-05-01en
dc.identifier.issn15459993en
dc.identifier.pmid23584453en
dc.identifier.doi10.1038/nsmb2557en
dc.identifier.urihttp://hdl.handle.net/10754/562754en
dc.description.abstractControl mechanisms that prevent aberrant signaling are necessary to maintain cellular homeostasis. We describe a new mechanism by which the adaptor protein Shc directly binds the MAP kinase Erk, thus preventing its activation in the absence of extracellular stimuli. The Shc-Erk complex restricts Erk nuclear translocation, restraining Erk-dependent transcription of genes, including those responsible for oncogenic growth. The complex forms through unique binding sites on both the Shc PTB domain and the N-terminal lobe of Erk. Upon receptor tyrosine kinase stimulation, a conformational change within Shc - induced through interaction with the phosphorylated receptor - releases Erk, allowing it to fulfill its role in signaling. Thus, in addition to its established role in promoting MAP kinase signaling in stimulated cells, Shc negatively regulates Erk activation in the absence of growth factors and thus could be considered a tumor suppressor in human cells. © 2013 Nature America, Inc. All rights reserved.en
dc.publisherNature Publishing Groupen
dc.titleInteraction with Shc prevents aberrant Erk activation in the absence of extracellular stimulien
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentBioscience Programen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentStructural Biology and Engineeringen
dc.identifier.journalNature Structural and Molecular Biologyen
dc.contributor.institutionDepartment of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX, United Statesen
dc.contributor.institutionGraduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center, Houston, TX, United Statesen
dc.contributor.institutionProtein Purification Facility, London Research Institute, Cancer Research UK, London, United Kingdomen
dc.contributor.institutionDepartment of Biology and Biochemistry, University of Bath, Bath, United Kingdomen
dc.contributor.institutionDepartment of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX, United Statesen
dc.contributor.institutionCenter for Biomolecular Structure and Function, University of Texas MD Anderson Cancer Center, Houston, TX, United Statesen
kaust.authorArold, Stefan T.en
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