Spatial and Temporal Regulation of Receptor Tyrosine Kinase Activation and Intracellular Signal Transduction
| Autor: | Michel Dominguez, Sophie Dahan, John J.M. Bergeron, Barry I. Posner, Gianni M. Di Guglielmo |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Endosome Endosomes Protein tyrosine phosphatase Biochemistry Receptor tyrosine kinase 03 medical and health sciences 0302 clinical medicine Humans Insulin Phosphorylation Feedback Physiological Epidermal Growth Factor biology Cell Membrane Autophosphorylation Intracellular Membranes Protein-Tyrosine Kinases Endocytosis Cell biology ErbB Receptors Intracellular signal transduction Protein Transport Insulin receptor 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis biology.protein Protein Tyrosine Phosphatases Signal transduction Tyrosine kinase Signal Transduction |
| Zdroj: | Annual Review of Biochemistry. 85:573-597 |
| ISSN: | 1545-4509 0066-4154 |
| DOI: | 10.1146/annurev-biochem-060815-014659 |
| Popis: | Epidermal growth factor (EGF) and insulin receptor tyrosine kinases (RTKs) exemplify how receptor location is coupled to signal transduction. Extracellular binding of ligands to these RTKs triggers their concentration into vesicles that bud off from the cell surface to generate intracellular signaling endosomes. On the exposed cytosolic surface of these endosomes, RTK autophosphorylation selects the downstream signaling proteins and lipids to effect growth factor and polypeptide hormone action. This selection is followed by the recruitment of protein tyrosine phosphatases that inactivate the RTKs and deliver them by membrane fusion and fission to late endosomes. Coincidentally, proteinases inside the endosome cleave the EGF and insulin ligands. Subsequent inward budding of the endosomal membrane generates multivesicular endosomes. Fusion with lysosomes then results in RTK degradation and downregulation. Through the spatial positioning of RTKs in target cells for EGF and insulin action, the temporal extent of signaling, attenuation, and downregulation is regulated. |
| Databáze: | OpenAIRE |
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