Phosphorylation of threonine residues on Shc promotes ligand binding and mediates crosstalk between MAPK and Akt pathways in breast cancer cells
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Type
ArticleAuthors
Suen, K.M.Lin, C.C.
Seiler, C.
George, R.
Poncet-Montange, G.
Biter, A.B.
Ahmed, Z.
Arold, Stefan T.

Ladbury, J.E.
KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Computational Bioscience Research Center (CBRC)
Date
2017-12-06Online Publication Date
2017-12-06Print Publication Date
2018-01Permanent link to this record
http://hdl.handle.net/10754/626378
Metadata
Show full item recordAbstract
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.Citation
Suen KM, Lin CC, Seiler C, George R, Poncet-Montange G, et al. (2017) Phosphorylation of threonine residues on Shc promotes ligand binding and mediates crosstalk between MAPK and Akt pathways in breast cancer cells. The International Journal of Biochemistry & Cell Biology. Available: http://dx.doi.org/10.1016/j.biocel.2017.11.014.Sponsors
We are grateful to Dr. David Hawke for his assistance in proteomics analysis.Publisher
Elsevier BVPubMed ID
29208567Additional Links
http://www.sciencedirect.com/science/article/pii/S1357272517303059ae974a485f413a2113503eed53cd6c53
10.1016/j.biocel.2017.11.014
Scopus Count
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