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VEGFR-2 Transmembrane domain This is a transmembrane domain (TMD) of vascular endothelial growth factor receptor 2 which regulates blood vessel homeostasis. Transmembrane signalling by receptor tyrosine kinases (RTKs) requires specific orientation of the intracellular kinase domains in active receptor dimers. Two mutants in VEGFR-2 TMD showed constitutive kinase activity, suggesting that precise TMD orientation is mandatory for kinase activation. Scanning mutagenesis and structural analysis indicated that introducing two polar amino acids in distinct positions of the TMD (G770E/F777E and I771E/L778E mutations) reorients transmembrane helices and leads to stable dimer formation. Therefore, it has been suggested that the transition between the inactive and the active dimeric state of VEGFR-2 implicates alternative dimeric TMD conformations.
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PubMed References
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Jiyao W et al.(2023). "The conserved domain database in 2023.",