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The ShcD phosphotyrosine adaptor subverts canonical EGF receptor trafficking.
- Source :
- Journal of Cell Science; 2017, Vol. 130 Issue 17, p2808-2820, 13p
- Publication Year :
- 2017
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- PHOSPHOTYROSINE
EPIDERMAL growth factor receptors
CLATHRIN
Subjects
Details
- Language :
- English
- ISSN :
- 00219533
- Volume :
- 130
- Issue :
- 17
- Database :
- Complementary Index
- Journal :
- Journal of Cell Science
- Publication Type :
- Academic Journal
- Accession number :
- 125066524
- Full Text :
- https://doi.org/10.1242/jcs.198903