Phosphorylation of threonine residues on Shc promotes ligand binding and mediates crosstalk between MAPK and Akt pathways in breast cancer cells

Handle URI:
http://hdl.handle.net/10754/626378
Title:
Phosphorylation of threonine residues on Shc promotes ligand binding and mediates crosstalk between MAPK and Akt pathways in breast cancer cells
Authors:
Suen, K.M.; Lin, C.C.; Seiler, C.; George, R.; Poncet-Montange, G.; Biter, A.B.; Ahmed, Z.; Arold, Stefan T. ( 0000-0001-5278-0668 ) ; Ladbury, J.E.
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC)
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.
Publisher:
Elsevier BV
Journal:
The International Journal of Biochemistry & Cell Biology
Issue Date:
6-Dec-2017
DOI:
10.1016/j.biocel.2017.11.014
Type:
Article
ISSN:
1357-2725
Sponsors:
We are grateful to Dr. David Hawke for his assistance in proteomics analysis.
Additional Links:
http://www.sciencedirect.com/science/article/pii/S1357272517303059
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorSuen, K.M.en
dc.contributor.authorLin, C.C.en
dc.contributor.authorSeiler, C.en
dc.contributor.authorGeorge, R.en
dc.contributor.authorPoncet-Montange, G.en
dc.contributor.authorBiter, A.B.en
dc.contributor.authorAhmed, Z.en
dc.contributor.authorArold, Stefan T.en
dc.contributor.authorLadbury, J.E.en
dc.date.accessioned2017-12-14T12:34:04Z-
dc.date.available2017-12-14T12:34:04Z-
dc.date.issued2017-12-06en
dc.identifier.citationSuen 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.en
dc.identifier.issn1357-2725en
dc.identifier.doi10.1016/j.biocel.2017.11.014en
dc.identifier.urihttp://hdl.handle.net/10754/626378-
dc.description.abstractScaffold 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.en
dc.description.sponsorshipWe are grateful to Dr. David Hawke for his assistance in proteomics analysis.en
dc.publisherElsevier BVen
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S1357272517303059en
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in The International Journal of Biochemistry & Cell Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in The International Journal of Biochemistry & Cell Biology, 5 December 2017. DOI: 10.1016/j.biocel.2017.11.014. © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectSignal transduction Serine threonine phosphorylation Erk Canceren
dc.titlePhosphorylation of threonine residues on Shc promotes ligand binding and mediates crosstalk between MAPK and Akt pathways in breast cancer cellsen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalThe International Journal of Biochemistry & Cell Biologyen
dc.eprint.versionPost-printen
dc.contributor.institutionGraduate School of Biological Sciences, The University of Texas MD Anderson Cancer Center, Unit 1954, 1515 Holcombe Blvd, Houston, TX 77030, USAen
dc.contributor.institutionDepartment of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Unit 1954, 1515 Holcombe Blvd, Houston, TX 77030, USAen
dc.contributor.institutionSchool of Molecular and Cellular Biology, University of Leeds, LC Miall Building, Leeds, LS2 9JT, UKen
dc.contributor.institutionStructural Biology STP, The Francis Crick Institute, Lincolns Inn Fields Laboratory, 44 Lincolns Inn Fields, Holborn, London, WC2A 3LY, UKen
dc.contributor.institutionOrthogon Therapeutics, 960 Turnpike Street, Unit 10, Canton, MA 02021, USAen
dc.contributor.institutionSabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, 1102 Bates Avenue, Houston, TX 77030, USAen
kaust.authorArold, Stefan T.en
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