Sandbox Reserved 1490: Difference between revisions
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It acts as cell-surface receptor for the ligands ANGPT1, ANGPT2 and ANGPT4 and regulates among others angiogenesis, endothelial cell survival and maintenance of vascular quiescence. It is important in the regulation of both normal physiologic and pathologic angiogenesis. The later is a fundamental step in the transition of tumors from a benign state to a malignant one. | It acts as cell-surface receptor for the ligands ANGPT1, ANGPT2 and ANGPT4 and regulates among others angiogenesis, endothelial cell survival and maintenance of vascular quiescence. It is important in the regulation of both normal physiologic and pathologic angiogenesis. The later is a fundamental step in the transition of tumors from a benign state to a malignant one. | ||
Angiogenesis is the process in which new blood vessels are formed from pre-existing blood vessels. The growth of these new blood vessels requires migration and proliferation of endothelial cells (ECs). It is an event controlled by angiogenic growth factors such as vascular endothelial growth factor (VEGF). | |||
While ANGPT1 is a TIE2 agonist and has a higher binding affinity to it than ANGPT2, ANGPT2 can act as a context-dependent agonist. Thus, the ANGPT/TIE2 kinase signaling pathway is an attractive anti-vascular target. | While ANGPT1 is a TIE2 agonist and has a higher binding affinity to it than ANGPT2, ANGPT2 can act as a context-dependent agonist. Thus, the ANGPT/TIE2 kinase signaling pathway is an attractive anti-vascular target. | ||
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Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-992 on the kinase activation loop. | Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-992 on the kinase activation loop. | ||
[[Image:Réaction Phosphorylation.jpg]] | [[Image:Réaction Phosphorylation.jpg]] | ||
''Fig 2. Phosphorylation reaction'' | ''Fig 2. Phosphorylation reaction'' | ||
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===• Description of total protein=== | ===• Description of total protein=== | ||
[[Image:TIE2 Schema.jpg]] | [[Image:TIE2 Schema.jpg]] | ||
''Fig 3. Scheme of the whole TIE2 receptor'' | ''Fig 3. Scheme of the whole TIE2 receptor'' | ||
====Important sites ==== | ====Important sites ==== | ||
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[[Image:electro.png]] | [[Image:electro.png]] | ||
''Fig 6. Western blot of p-TIE2 in Human Endothelial Cells transfected with TIE2-WT (Wild type) or with mutant TIE2 (L914F). Tubulin served as loading control. The hyperphosphorylation is clearly visible.''<ref>PMID:26258417</ref> | ''Fig 6. Western blot of p-TIE2 in Human Endothelial Cells transfected with TIE2-WT (Wild type) or with mutant TIE2 (L914F). Tubulin served as loading control. The hyperphosphorylation is clearly visible.''<ref name="Molecular Therapies">PMID: 26258417</ref> | ||
Thus, genetic and transplantation‐based models offer versatile tools to study the pathology of VMs, as well as the efficacy and safety of potential molecular therapies. | Thus, genetic and transplantation‐based models offer versatile tools to study the pathology of VMs, as well as the efficacy and safety of potential molecular therapies. | ||
Rapamycin is the first molecular therapy for VMs. It is currently being tested in a multicenter clinical trial on lymphatico-vascular malformations.<ref | Rapamycin is the first molecular therapy for VMs. It is currently being tested in a multicenter clinical trial on lymphatico-vascular malformations.<ref name="Molecular Therapies"/> | ||
[[Image:lesion area.png]] | [[Image:lesion area.png]] | ||
''Fig 7. (C) HUVECs lesional area measured every 2 days for 16 days. (D) Vascular volume at day 15 measured by analysis of color Doppler 3D image stacks. When compared with the vehicle-treated group, the lesional area was significantly smaller in the rapamycin-treated group from day 4 to day 16 and in the TIE2-TKI–treated group from day 8 to day 14.''<ref | ''Fig 7. (C) HUVECs lesional area measured every 2 days for 16 days. (D) Vascular volume at day 15 measured by analysis of color Doppler 3D image stacks. When compared with the vehicle-treated group, the lesional area was significantly smaller in the rapamycin-treated group from day 4 to day 16 and in the TIE2-TKI–treated group from day 8 to day 14.''<ref name="Molecular Therapies"/> | ||
===•Cancers=== | ===•Cancers=== | ||
