Sandbox Reserved 1490: Difference between revisions
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{{Sandbox_Reserved_ESBS}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | {{Sandbox_Reserved_ESBS}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | ||
==Crystal structure of cytoplasmic kinase domain of Tie2 in complex with decipera compound DP1919== | ==Crystal structure of cytoplasmic kinase domain of Tie2 in complex with decipera compound DP1919== | ||
< | <StructureSection load='6mwe' size='340' side='right' caption='Caption for this structure' scene=''> | ||
The protein we are focusing one is a protein kinase receptor to a family of ligands called angiopoietins. This receptor is a Tyrosine Kinase TIE2. We are going to analyze the <scene name='80/802664/Entire_molecule/1'>kinase domain</scene> of this protein. | The protein we are focusing one is a protein kinase receptor to a family of ligands called angiopoietins. This receptor is a Tyrosine Kinase TIE2. We are going to analyze the <scene name='80/802664/Entire_molecule/1'>kinase domain</scene> of this protein. | ||
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[[Image:controlANG.png]] | [[Image:controlANG.png]] | ||
''Fig 1. These cells express Tie2 and are marked with GFP. They were incubated with vehicle (control; left column) and COMP–Ang1 (right column). The scale bars represent 10 μm.''<ref>PMID:19223473</ref> | ''Fig 1. These cells express Tie2 and are marked with GFP. They were incubated with vehicle (control; left column) and COMP–Ang1 (right column). The scale bars represent 10 μm.''<ref>PMID:19223473</ref> | ||
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ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein] | ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein] | ||
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'' | |||
===• 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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– Transmembrane region : AA 749 to 769 | – Transmembrane region : AA 749 to 769 | ||
– Cytoplasmic region : AA 770 to 1124 (already found 3D structures: [[1fvr]], [[2oo8]], [[2osc]], [[2wqb]], [[3bea]], [[3l8p]], [[4x3j]] | – Cytoplasmic region : AA 770 to 1124 (already found 3D structures: [[1fvr]], [[2oo8]], [[2osc]], [[2wqb]], [[3bea]], [[3l8p]], [[4x3j]] | ||
====Domains ==== | ====Domains ==== | ||
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[[Image:Venous Malformations Diagram.jpg]] | [[Image:Venous Malformations Diagram.jpg]] | ||
''Fig 4. Diagram : Comparison of the Kinase Activities of Normal and Mutant TIE2 Receptors. (B) Cells infected with wild-type baculovirus (wt) or virus expressing normal TIE2 (R2) or mutant TIE2 (W2). Cells expressing the mutation at position 849 (Arginine → Tryptophan) have an autophosphorylation activity 6 to 10 times higher than wild cells.''<ref>PMID:8980225</ref> | ''Fig 4. Diagram : Comparison of the Kinase Activities of Normal and Mutant TIE2 Receptors. (B) Cells infected with wild-type baculovirus (wt) or virus expressing normal TIE2 (R2) or mutant TIE2 (W2). Cells expressing the mutation at position 849 (Arginine → Tryptophan) have an autophosphorylation activity 6 to 10 times higher than wild cells.''<ref>PMID:8980225</ref> | ||
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[[Image:Venous Malformations Immunohistochemistry.jpg]] | [[Image:Venous Malformations Immunohistochemistry.jpg]] | ||
''Fig 5. Pictures of immunohistochemistry of VMs with Antibodies against Smooth Muscle Cells 𝛂-Actin <ref>PMID:8980225</ref>'' | ''Fig 5. Pictures of immunohistochemistry of VMs with Antibodies against Smooth Muscle Cells 𝛂-Actin <ref>PMID:8980225</ref>'' | ||
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[[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>PMID:26258417</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>PMID:26258417</ref> | ||