原创力文档the eya tyrosine phosphatase activity is pro-angiogenic and is inhibited by benzbromaroneeya酪氨酸磷酸酶活动由benzbromarone pro-angiogenic并抑制.pdfVIP
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the eya tyrosine phosphatase activity is pro-angiogenic and is inhibited by benzbromaroneeya酪氨酸磷酸酶活动由benzbromarone pro-angiogenic并抑制
The EYA Tyrosine Phosphatase Activity Is Pro-Angiogenic
and Is Inhibited by Benzbromarone
1 1 1 1 1,2,4
Emmanuel Tadjuidje , Tim Sen Wang , Ram Naresh Pandey , Saulius Sumanas , Richard A. Lang ,
Rashmi S. Hegde1,3*
1 Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America, 2 The Visual Systems Group, Division of
Pediatric Ophthalmology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America, 3 Department of Pediatrics, University of Cincinnati,
Cincinnati, Ohio, United States of America, 4 Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America
Abstract
Eyes Absents (EYA) are multifunctional proteins best known for their role in organogenesis. There is accumulating evidence
that overexpression of EYAs in breast and ovarian cancers, and in malignant peripheral nerve sheath tumors, correlates with
tumor growth and increased metastasis. The EYA protein is both a transcriptional activator and a tyrosine phosphatase, and
the tyrosine phosphatase activity promotes single cell motility of mammary epithelial cells. Since EYAs are expressed in
vascular endothelial cells and cell motility is a critical feature of angiogenesis we investigated the role of EYAs in this
process. Using RNA interference techniques we show that EYA3 depletion in human umbilical vein endothelial cells inhibits
transwell migration as well as Matrigel-induced tube formation. To specifically query the role of the EYA tyrosine
phosphatase activity we employed a chemical biology approach. Through an experim
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