SHIP2 (SH2 domain-containing inositol phosphatase 2) SH2 domain negatively controls SHIP2 monoubiquitination in response to epidermal growth factor
| Autor: | Isabelle Pirson, Virginie Imbault, Aude Guillabert, David Communi, Julie De Schutter, Christophe Erneux, Chantal Degraef |
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| Rok vydání: | 2009 |
| Předmět: |
Time Factors
Ubiquitin binding Nedd4 Ubiquitin Protein Ligases Amino Acid Motifs Epidermal Growth Factor -- pharmacology SH2 domain Biochemistry Ubiquitin Epidermal growth factor Protein Structure Tertiary -- physiology Chlorocebus aethiops Monoubiquitination Proto-Oncogene Proteins c-cbl Proto-Oncogene Proteins c-cbl -- metabolism biology Mechanisms of Signal Transduction Sciences bio-médicales et agricoles Phosphoric Monoester Hydrolases -- genetics Cell biology Ubiquitin ligase Ubiquitin-Protein Ligases -- genetics Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases COS Cells Proteasome Endopeptidase Complex Ubiquitin-Protein Ligases Models Biological Cercopithecus aethiops Ubiquitination -- physiology Proteasome Endopeptidase Complex -- metabolism Proteasome Endopeptidase Complex -- genetics Animals Humans Molecular Biology Epidermal Growth Factor -- metabolism Endosomal Sorting Complexes Required for Transport -- metabolism Endosomal Sorting Complexes Required for Transport Epidermal Growth Factor Ubiquitination -- drug effects Ubiquitination Cell Biology Amino Acid Motifs -- physiology Ubiquitin-Protein Ligases -- metabolism Phosphoric Monoester Hydrolases Protein Structure Tertiary Proteasome Proto-Oncogene Proteins c-cbl -- genetics Endosomal Sorting Complexes Required for Transport -- genetics biology.protein Phosphoric Monoester Hydrolases -- metabolism |
| Zdroj: | The Journal of biological chemistry, 284 (52 |
| ISSN: | 1083-351X |
| Popis: | The SH2 domain containing inositol 5-phosphatase SHIP2 contains several interacting domains that are important for scaffolding properties. We and others have previously reported that SHIP2 interacts with the E3 ubiquitin ligase c-Cbl. Here, we identified human SHIP2 monoubiquitination on lysine 315. SHIP2 could also be polyubiquitinated but was not degraded by the 26 S proteasome. Furthermore, we identified a ubiquitin-interacting motif at the C-terminal end of SHIP2 that confers ubiquitin binding capacity. However, this ubiquitin-interacting motif is dispensable for its monoubiquitination. We showed that neither c-Cbl nor Nedd4-1 play the role of ubiquitin ligase for SHIP2. Strikingly, monoubiquitination of the DeltaSH2-SHIP2 mutant (lacking the N-terminal SH2 domain) is strongly increased, suggesting an intrinsic inhibitory effect of the SHIP2 SH2 domain on its monoubiquitination. Moreover, SHIP2 monoubiquitination was increased upon 30 min of epidermal growth factor stimulation. This correlates with the loss of interaction between the SHIP2 SH2 domain and c-Cbl. In this model, c-Cbl could mask the monoubiquitination site and thereby prevent SHIP2 monoubiquitination. The present study thus reveals an unexpected and novel role of SHIP2 SH2 domain in the regulation of its newly identified monoubiquitination. Journal Article Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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