The insulin-like growth factor 1 (IGF-1) receptor is a substrate for gamma-secretase-mediated intramembrane proteolysis
| Autor: | James C. Powell, Brian McElroy, Justin V. McCarthy |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Biophysics
Kidney Biochemistry Regulated Intramembrane Proteolysis Receptor tyrosine kinase Cell Line Receptor IGF Type 1 Substrate Specificity Mice Growth factor receptor Amyloid precursor protein Animals Humans APH-1 Molecular Biology Gamma secretase Insulin-like growth factor 1 receptor Mice Knockout biology Cell Membrane Presenilins Cell Biology IRS2 Cell biology Enzyme Activation biology.protein Amyloid Precursor Protein Secretases Peptide Hydrolases |
| Zdroj: | Biochemical and biophysical research communications. 358(4) |
| ISSN: | 0006-291X |
| Popis: | Several type-1 membrane proteins undergo regulated intramembrane proteolysis resulting in the generation of biologically active protein fragments. Presenilin-dependant gamma-secretase activity is central to this event and includes amyloid precursor protein (APP), Notch and ErbB4 as substrates. Here we show that the insulin-like growth factor 1 receptor (IGF-IR) undergoes regulated intramembrane proteolysis. A metalloprotease-dependant ectodomain-shedding event generates a approximately 52 kDa IGF-IR-carboxyl terminal domain (CTD). The IGF-IR-CTD is consequentially a substrate for gamma-secretase cleavage, liberating a approximately 50 kDa intracellular domain (ICD) that can be inhibited by a specific gamma-secretase inhibitor. This study suggests that the IGF-IR is a substrate for gamma-secretase and may mediate a function independent of its role as a receptor tyrosine kinase. |
| Databáze: | OpenAIRE |
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