CCL

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001-es BibID:BIBFORM004734
Első szerző:Mosesson, Yaron
Cím:Endocytosis of receptor tyrosine kinases is driven by monoubiquitylation, not polyubiquitylation / Mosesson, Y., Shtiegman, K., Katz, M., Zwang, Y., Vereb, G., Szollosi, J., Yarden, Y.
Dátum:2003
ISSN:021-9258 (Print)
Megjegyzések:Growth factors stimulate specific receptor tyrosine kinases, but subsequent receptor endocytosis terminates signaling. The ubiquitin ligase c-Cbl targets epidermal growth factor receptors (EGFRs) to endocytosis by tagging them with multiple ubiquitin molecules. However, the type of ubiquitylation is unknown; whereas polyubiquitin chains signal proteasomal degradation, ubiquitin monomers control other processes. We report that in isolation c-Cbl mediates monoubiquitylation rather than polyubiquitylation of EGFRs. Consistent with the sufficiency of monoubiquitylation, when fused to the tail of EGFR, a single ubiquitin induces receptor endocytosis and degradation in cells. By using receptor and ubiquitin mutants, we infer that c-Cbl attaches a founder monoubiquitin to the kinase domain of EGFR and this is complemented by the conjugation of additional monoubiquitins. Hence, receptor tyrosine kinases are desensitized through conjugation of multiple monoubiquitins, which is distinct from polyubiquitin-dependent proteasomal degradation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Animals
Cells
chemistry
Cho Cells
Cricetinae
Electrophoresis,Polyacrylamide Gel
Endocytosis
Epidermal Growth Factor
Genetic Vectors
Immunoblotting
Ligases
metabolism
Mice
Microscopy,Fluorescence
Plasmids
Precipitin Tests
Protein Structure,Tertiary
Protein-Tyrosine Kinases
Proteins
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-cbl
Receptor Protein-Tyrosine Kinases
Research
Support
Time Factors
Transfection
Ubiquitin
Ubiquitin-Protein Ligases
Megjelenés:The Journal of Biological Chemistry. - 278 : 24 (2003), p. 21323-21326. -
További szerzők:Shtiegman, K. Katz, M. Zwang, Y. Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus) Yarden, Yosef
Internet cím:elektronikus változat
elektronikus változat
DOI
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