Grb2 monomer–dimer equilibrium determines normal versus oncogenic function

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dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber6en_US
dc.contributor.authorAhmed, Zamalen_US
dc.contributor.authorTimsah, Zahraen_US
dc.contributor.authorSuen, Kin M.en_US
dc.contributor.authorCook, Nathan P.en_US
dc.contributor.authorLee, Gilbert R. IVen_US
dc.contributor.authorLin, Chi-Chuanen_US
dc.contributor.authorGagea, Mihaien_US
dc.contributor.authorMarti, Angel A.en_US
dc.contributor.authorLadbury, John E.en_US
dc.date.accessioned2016-01-29T21:44:39Zen_US
dc.date.available2016-01-29T21:44:39Zen_US
dc.date.issued2015en_US
dc.description.abstractThe adaptor protein growth factor receptor-bound protein 2 (Grb2) is ubiquitously expressed in eukaryotic cells and involved in a multitude of intracellular protein interactions. Grb2 plays a pivotal role in tyrosine kinase-mediated signal transduction including linking receptor tyrosine kinases to the Ras/mitogen-activated protein (MAP) kinase pathway, which is implicated in oncogenic outcome. Grb2 exists in a constitutive equilibrium between monomeric and dimeric states. Here we show that only monomeric Grb2 is capable of binding to SOS and upregulating MAP kinase signalling and that the dimeric state is inhibitory to this process. Phosphorylation of tyrosine 160 (Y160) on Grb2, or binding of a tyrosylphosphate-containing ligand to the SH2 domain of Grb2, results in dimer dissociation. Phosphorylation of Y160 on Grb2 is readily detectable in the malignant forms of human prostate, colon and breast cancers. The self-association/dissociation of Grb2 represents a switch that regulates MAP kinase activity and hence controls cancer progression.en_US
dc.identifier.citationAhmed, Zamal, Timsah, Zahra, Suen, Kin M., et al.. "Grb2 monomer–dimer equilibrium determines normal versus oncogenic function." <i>Nature Communications,</i> 6, (2015) Macmillan Publishers Limited: http://dx.doi.org/10.1038/ncomms8354.en_US
dc.identifier.doihttp://dx.doi.org/10.1038/ncomms8354en_US
dc.identifier.urihttps://hdl.handle.net/1911/88280en_US
dc.language.isoengen_US
dc.publisherMacmillan Publishers Limiteden_US
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article?s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.?en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleGrb2 monomer–dimer equilibrium determines normal versus oncogenic functionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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