Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli
Type
ArticleAuthors
Suen, KinManLin, Chichuan
George, Roger R.
Melo, Fernando A.
Biggs, Eleanor R.
Ahmed, Zamal
Drake, Melanie N.
Arur, Swathi
Arold, Stefan T.

Ladbury, John E S D
KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Computational Bioscience Research Center (CBRC)
Structural Biology and Engineering
Date
2013-05-01Permanent link to this record
http://hdl.handle.net/10754/562754
Metadata
Show full item recordAbstract
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.Publisher
Nature Publishing GroupPubMed ID
23584453ae974a485f413a2113503eed53cd6c53
10.1038/nsmb2557
Scopus Count
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