Growth factors: Difference between revisions
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Each monomer contains a central antiparallel beta sheet, with the canonical <scene name='41/411433/Knot_new/3'>cysteine knot </scene> found in other VEGFs. <ref>PMID:1396586</ref> The knot consists of an eight residue ring formed by the backbone of residues 57-61 and 102-104 and intramolecular disulfide bridges Cys57-Cys102 and Cys61-Cys104, and a third bridge, Cys26-Cys68, that passes perpendicularly through the ring. Each VEGF-E monomer contains an amino terminal alpha helix and three solvent accessible loop regions, L2, <scene name='41/411433/Vegf-e_l1_l3/3'>L1 and L3 </scene>. | Each monomer contains a central antiparallel beta sheet, with the canonical <scene name='41/411433/Knot_new/3'>cysteine knot </scene> found in other VEGFs. <ref>PMID:1396586</ref> The knot consists of an eight residue ring formed by the backbone of residues 57-61 and 102-104 and intramolecular disulfide bridges Cys57-Cys102 and Cys61-Cys104, and a third bridge, Cys26-Cys68, that passes perpendicularly through the ring. Each VEGF-E monomer contains an amino terminal alpha helix and three solvent accessible loop regions, L2, <scene name='41/411433/Vegf-e_l1_l3/3'>L1 and L3 </scene>. | ||
are able to form a complex hydrogen bond network as well as extensive hydrophobic contacts with VEGFR making these loops ideal receptor specificity determinants. Residues: P34, S36, T43, P50, R46, D63, E64, and E67 make up the <scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_binding_site/1'>VEGF-E binding pocket </scene>and are critical for binding to VEGFR-2 as determined by alanine mutagenesis.<ref> PMID:16672228</ref> Further, the salt bridge between <scene name='41/411433/Vegf-e_salt_bridge/4'>R46 and E64 </scene> is believed to be the source of VEGF-E’s VEGFR-2 specificity by preventing binding to VEGFR-1. <ref>PMID:15272021</ref> | are able to form a complex hydrogen bond network as well as extensive hydrophobic contacts with VEGFR making these loops ideal receptor specificity determinants. Residues: P34, S36, T43, P50, R46, D63, E64, and E67 make up the <scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_binding_site/1'>VEGF-E binding pocket </scene>and are critical for binding to VEGFR-2 as determined by alanine mutagenesis.<ref> PMID:16672228</ref> Further, the salt bridge between <scene name='41/411433/Vegf-e_salt_bridge/4'>R46 and E64 </scene> is believed to be the source of VEGF-E’s VEGFR-2 specificity by preventing binding to VEGFR-1. <ref>PMID:15272021</ref> | ||
[[Vascular Endothelial Growth Factor Receptor]]s (VEGFRs) are [[tyrosine kinase receptors]] responsible for binding with [[VEGF]] to initiate signal cascades that stimulate angiogenesis among other effects. The tyrosine kinase domain of VEGFR-2 is separated into 2 segments with a 70 amino acid long kinase insert region. Upon binding VEGFA and subsequent dimerization, VEGFR-2 is autophosphoryalted at the carboxy terminal tail and kinase insert region, 6 tyrosine residues of VEGFR2 are autophosphorylated. <scene name='41/411436/Cv/2'>Auto-phosphorylation of residues 1054 and 1059</scene> within the activation loop of VEGFR2 leads to increased kinase activity. <scene name='41/411436/Cv/4'>Anti-tumor inhibitor binding site</scene> ([[3c7q]]). | |||
See also [[Bevacizumab]]. | |||
*[[TGF-beta receptor|Transforming Growth Factor and its receptor]] | *[[TGF-beta receptor|Transforming Growth Factor and its receptor]] | ||