Toward Understanding the Functional State of the Grb7 Protein

Abstract

Human growth factor receptor bound protein 7 (Grb7) proteins are the family of adaptor proteins that include Grb7, Grb10 and Grb14. These proteins have a conserved topology that includes a proline rich N‐terminal domain, an RA domain, a PH domain and a C‐terminal SH2 domain. Grb7 proteins bind with activated receptor tyrosine kinase (RTK) receptors through their SH2 domain to mediate downstream signal transduction events. Previous studies in our laboratory have shown the Grb7SH2 domain exists in a dimeric form and this may control the dimerization of the full‐length protein (FLGrb7). In our current studies, we show a FLGrb7 phosphorylation mimic, Y492E‐FLGrb7, results in a monomeric form of the protein, by in vitro biophysical measurements. Specifically, size exclusion and analytical ultracentrifugation results demonstrate Y492E‐FLGrb7 is essentially monomeric, while under the same conditions wild‐type Grb7 (WTFLGrb7) exists as a dimer. Further, the size and shape of these proteins were determined through dynamic light scattering measurements. These studies suggest the phosphorylation mimic Y492E‐FLGrb7 may exist in a more open, as opposed to compact globular, conformational form. We interpret the above results with a view towards understanding the functional state of Grb7 protein, and its role in controlling cell signaling pathways via interaction with its binding partners.Support or Funding InformationNIH5‐SC3‐6M116728This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.