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Tryptophan 387 and 390 residues in ADAMTS13 are crucial to the ability of vascular tube formation and cell migration of endothelial cells
Author(s) -
Liu Ling,
Ma Zhenni,
Zhou Xuemei,
Yin Jie,
Lu Jun,
Su Jian,
Shen Fei,
Xie Liqian,
Hu Shaoyan,
Ling Jing
Publication year - 2020
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13313
Subject(s) - chemistry , disintegrin , secretion , von willebrand factor , adamts13 , mutant , tryptophan , thrombospondin , microbiology and biotechnology , biochemistry , metalloproteinase , medicine , matrix metalloproteinase , amino acid , platelet , biology , gene
Abstract A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) was mainly generated and secreted from endothelial cells (ECs). Our previous study showed that tryptophan (Trp) residues at 387 and 390 in ADAMTS13 are required for its secretion and enzymatic activity. However, the effects on its host cell as well as the potential mechanism have not been clear. The aim of the study was to examine the effects of Trp residues 387 and 390 of ADAMTS13 on the biological processes of ECs. Herein, Trp was substituted with alanine in ADAMTS13 to generate ADAMTS13 mutants at 387 (W387A), 390 (W390A), and double mutants at 387 and 390 (2WA), respectively. We found that substitution mutation impaired vascular endothelial growth factor (VEGF) secretion and the downstream JAK1/STAT3 activation, the binding ability to Von Willebrand factor, cell proliferation, migration, and vascular tube formation. Overall, our study concluded that Trp 387 and Trp 390 of ADAMTS13 play vital roles in the biological function of ECs.