Sandbox Reserved 1490: Difference between revisions
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– '''Mutation in position 849 : Arginine → Tryptophane:''' Change from large size and basic (R) to large size and aromatic (W). Increased autophosphorylation and kinase activation; no effect on location at membrane. | – '''Mutation in position 849 : Arginine → Tryptophane:''' Change from large size and basic (R) to large size and aromatic (W). Increased autophosphorylation and kinase activation; no effect on location at membrane. | ||
Arginine at position 849 is found in six residues upstream of the invariant lysine K855 in the kinase domain (sequence preserved among the human, bovine, murine and rat TIE2 sequences). This seems to prove that a basic amino acid is essential for this position. In addition, arginine located a few amino acids before invariant lysine is involved in stabilizing the kinase domain (hydrogen binding of arginine with a proline downstream). It is therefore possible that R849 may also be involved in the stabilization of the kinase domain. Thus, the substitution of R849 by a W could modify the conformation of the kinase domain, leading to a decrease in inhibitory mechanisms and involving autophosphorylation.<ref>PMID:8980225</ref> | Arginine at position 849 is found in six residues upstream of the invariant lysine K855 in the kinase domain (sequence preserved among the human, bovine, murine and rat TIE2 sequences). This seems to prove that a basic amino acid is essential for this position. In addition, arginine located a few amino acids before invariant lysine is involved in stabilizing the kinase domain (hydrogen binding of arginine with a proline downstream). It is therefore possible that R849 may also be involved in the stabilization of the kinase domain. Thus, the substitution of R849 by a W could modify the conformation of the kinase domain, leading to a decrease in inhibitory mechanisms and involving autophosphorylation.<ref name="Vascular dysmorphogenesis">PMID: 8980225</ref> | ||
[[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 | ''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 name="Vascular dysmorphogenesis"/> | ||
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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 | ''Fig 5. Pictures of immunohistochemistry of VMs with Antibodies against Smooth Muscle Cells 𝛂-Actin <ref name="Vascular dysmorphogenesis"/>'' | ||
''B = Abnormal channels'' | ''B = Abnormal channels'' | ||