Product Reference
Cytosolic lysine residues enhance anterograde transport and activation of the erythropoietin receptor.
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| Author |
Liron Yosha,Orly Ravid,Nathalie Ben-Califa,Drorit Neumann |
| Citation Information |
The Biochemical journal, 435: (2011) |
| Keywords |
Animals,Cells, Cultured,Cytosol,Endoplasmic Reticulum,Humans,Lysine,Mice,Models, Biological,Mutant Proteins,Protein Processing, Post-Translational,Protein Transport,Receptors, Erythropoietin,Ubiquitination |
| Related Products |
05-777 |
| Pub Med ID |
21291419 |
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Abstract
Lysine residues are key residues in many cellular processes, in part due to their ability to accept a wide variety of post-translational modifications. In the present study, we identify the EPO-R [EPO (erythropoietin) receptor] cytosolic lysine residues as enhancers of receptor function. EPO-R drives survival, proliferation and differentiation of erythroid progenitor cells via binding of its ligand EPO. We mutated the five EPO-R cytosolic lysine residues to arginine residues (5KR EPO-R), eliminating putative lysine-dependent modifications. Overexpressed 5KR EPO-R displayed impaired ubiquitination and improved stability compared with wt (wild-type) EPO-R. Unexpectedly, fusion proteins consisting of VSVGtsO45 (vesicular stomatitis virus glycoprotein temperature-sensitive folding mutant) with wt or 5KR EPO-R cytosolic domains demonstrated delayed glycan maturation kinetics upon substitution of the lysine residues. Moreover, VSVG-wt EPO-R, but not VSVG-5KR EPO-R, displayed endoplasmic reticulum-associated ubiquitination. Despite similar cell-surface EPO-binding levels of both receptors and the lack of EPO-induced ubiquitination by 5KR EPO-R, the lysine-less mutant produced weaker receptor activation and signalling than the wt receptor. We thus propose that EPO-R cytosolic lysine residues enhance receptor function, most probably through ubiquitination and/or other post-translational modifications.
