The ShcD phosphotyrosine adaptor subverts canonical EGF receptor trafficking.

Shc family signalling adaptors connect activated transmembrane receptors to proximal effectors, and most also contain a sequence involved in clathrin-mediated receptor endocytosis. Notably, this AP2 adaptin-binding motif (AD) is absent from the ShcD (also known as Shc4) homolog, which also uniquely promotes ligand-independent phosphorylation of the epidermal growth factor receptor ...
(EGFR). We now report that cultured cells expressing ShcD exhibit reduced EGF uptake, commensurate with a decrease in EGFR surface presentation. Under basal conditions, ShcD colocalises with the EGFR and facilitates its phosphorylation, ubiquitylation and accumulation in juxtanuclear vesicles identified as Rab11-positive endocytic recycling compartments. Accordingly, ShcD also functions as a constitutive binding partner for the E3 ubiquitin ligase Cbl. EGFR phosphorylation and focal accumulation likewise occur upon ShcD co-expression in U87 glioma cells. Loss of ShcD phosphotyrosine-binding function or insertion of the ShcA AD sequence each restore ligand acquisition through distinct mechanisms. The AD region also contains a nuclear export signal, indicating its multifunctionality. Overall, ShcD appears to possess several molecular permutations that actively govern the EGFR, which may have implications in development and disease.
Mesh Terms:
Adaptor Protein Complex Subunits, Amino Acid Motifs, Cell Line, Tumor, Cell Membrane, Cell Nucleus, Cell Shape, Endocytosis, Epidermal Growth Factor, Glioma, Humans, Ligands, Phosphorylation, Phosphotyrosine, Protein Binding, Protein Domains, Protein Transport, Proto-Oncogene Proteins c-cbl, Receptor, Epidermal Growth Factor, Shc Signaling Adaptor Proteins, Subcellular Fractions, Transport Vesicles, Ubiquitination, rab GTP-Binding Proteins
J. Cell. Sci.
Date: Sep. 01, 2017
Download Curated Data For This Publication
212104
Switch View:
  • Interactions 3