title: PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.
abstract: Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.
authors.affiliation: Key Laboratory of Cardiovascular Remodelling and Function Research (Chinese Ministry of Education and Chinese Ministry of Health) and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodelling and Function Research (Chinese Ministry of Education and Chinese Ministry of Health) and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.affiliation: Key Laboratory of Cardiovascular Remodelling and Function Research (Chinese Ministry of Education and Chinese Ministry of Health) and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Key Laboratory of Cardiovascular Remodelling and Function Research (Chinese Ministry of Education and Chinese Ministry of Health) and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Cardiovascular Remodelling and Function Research (Chinese Ministry of Education and Chinese Ministry of Health) and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D050719:Crk-Associated Substrate Protein; C099818:DOCK1 protein, human; D004791:Enzyme Inhibitors; D051419:Paxillin; D040301:Vascular Endothelial Growth Factor Receptor-2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein