Browsing by Author "Lin, Chi-Chuan"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Grb2 monomer–dimer equilibrium determines normal versus oncogenic function
    (Macmillan Publishers Limited, 2015) Ahmed, Zamal; Timsah, Zahra; Suen, Kin M.; Cook, Nathan P.; Lee, Gilbert R. IV; Lin, Chi-Chuan; Gagea, Mihai; Marti, Angel A.; Ladbury, John E.
    The 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.