A role for the adaptor protein ShcD in epidermal growth factor receptor turnover
Receptor tyrosine kinase (RTK) endocytosis and degradation following ligand stimulation is essential for attenuation of signals, and disruption of proteins involved in receptor turnover leads to oncogenesis. Adaptor proteins play a central role in RTK endocytosis by recruiting further downstream proteins that can potentiate signaling. We have discovered a novel adaptor protein, ShcD, which binds both activated RTKs and components of the endocytic machinery. My graduate research investigates the role of ShcD in internalization of the epidermal growth factor receptor (EGFR). We found that ShcD is expressed in specific patterns in brain that overlap with regions of epidermal growth factor (EGF) expression, and that ShcD undergoes a partial nuclear translocation during differentiation of a neural cell line in culture. We found that the ShcD phosphotyrosine binding (PTB) domain interacts directly with two regions of EGFR. ShcD also interacts with the EGFR ubiquitin ligase, Cbl, in cells. Additionally, cells overexpressing ShcD display enhanced EGFR degradation independent of EGF stimulation, suggesting a role for ShcD as a positive regulator of EGFR degradation. Together, these data identify both a role for ShcD in EGFR turnover, and an organ system in which to further study the biological effect of this regulation.