Suen, KM, Lin, CC orcid.org/0000-0003-3071-172X, Seiler, C et al. (6 more authors) (2018) Phosphorylation of threonine residues on Shc promotes ligand binding and mediates crosstalk between MAPK and Akt pathways in breast cancer cells. International Journal of Biochemistry and Cell Biology, 94. pp. 89-97. ISSN 1357-2725
Abstract
Scaffold proteins play important roles in regulating signalling network fidelity, the absence of which is often the basis for diseases such as cancer. In the present work, we show that the prototypical scaffold protein Shc is phosphorylated by the extracellular signal-regulated kinase, Erk. In addition, Shc threonine phosphorylation is specifically up-regulated in two selected triple-negative breast cancer (TNBC) cell lines. To explore how Erk-mediated threonine phosphorylation on Shc might play a role in the dysregulation of signalling events, we investigated how Shc affects pathways downstream of EGF receptor. Using an in vitro model and biophysical analysis, we show that Shc threonine phosphorylation is responsible for elevated Akt and Erk signalling, potentially through the recruitment of the 14-3-3 ζ and Pin-1 proteins.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017, Elsevier Ltd. This is an author produced version of a paper published in The International Journal of Biochemistry & Cell Biology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Signal transduction; Serine threonine phosphorylation; Erk; Cancer |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Mechanistic Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 14 Dec 2017 13:50 |
Last Modified: | 05 Dec 2018 01:38 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.biocel.2017.11.014 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:125068 |
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Filename: Shc Thr phosphorylation_IJBCB_FINAL_161117.pdf
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