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dc.contributor.authorLai, Ju-Gengen_US
dc.contributor.authorTsai, Su-Meien_US
dc.contributor.authorTu, Hsiao-Chenen_US
dc.contributor.authorChen, Wen-Chuanen_US
dc.contributor.authorKou, Fong-Jien_US
dc.contributor.authorLu, Jeng-Weien_US
dc.contributor.authorWang, Horng-Daren_US
dc.contributor.authorHuang, Chou-Longen_US
dc.contributor.authorYuh, Chiou-Hwaen_US
dc.date.accessioned2014-12-08T15:36:41Z-
dc.date.available2014-12-08T15:36:41Z-
dc.date.issued2014-08-29en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0106129en_US
dc.identifier.urihttp://hdl.handle.net/11536/25046-
dc.description.abstractThe WNK1 (WNK lysine deficient protein kinase 1) protein is a serine/threonine protein kinase with emerging roles in cancer. WNK1 causes hypertension and hyperkalemia when overexpressed and cardiovascular defects when ablated in mice. In this study, the role of Wnk1 in angiogenesis was explored using the zebrafish model. There are two zebrafish wnk1 isoforms, wnk1a and wnk1b, and both contain all the functional domains found in the human WNK1 protein. Both isoforms are expressed in the embryo at the initiation of angiogenesis and in the posterior cardinal vein (PCV), similar to fms-related tyrosine kinase 4 (flt4). Using morpholino antisense oligonucleotides against wnk1a and wnk1b, we observed that wnk1 morphants have defects in angiogenesis in the head and trunk, similar to flk1/vegfr2 morphants. Furthermore, both wnk1a and wnk1b mRNA can partially rescue the defects in vascular formation caused by flk1/vegfr2 knockdown. Mutation of the kinase domain or the Akt/PI3K phosphorylation site within wnk1 destroys this rescue capability. The rescue experiments provide evidence that wnk1 is a downstream target for Vegfr2 (vascular endothelial growth factor receptor-2) and Akt/PI3K signaling and thereby affects angiogenesis in zebrafish embryos. Furthermore, we found that knockdown of vascular endothelial growth factor receptor-2 (flk1/vegfr2) or vascular endothelial growth factor receptor-3 (flt4/vegfr3) results in a decrease in wnk1a expression, as assessed by in situ hybridization and q-RT-PCR analysis. Thus, the Vegf/Vegfr signaling pathway controls angiogenesis in zebrafish via Akt kinase-mediated phosphorylation and activation of Wnk1 as well as transcriptional regulation of wnk1 expression.en_US
dc.language.isoen_USen_US
dc.titleZebrafish WNK Lysine Deficient Protein Kinase 1 (wnk1) Affects Angiogenesis Associated with VEGF Signalingen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0106129en_US
dc.identifier.journalPLOS ONEen_US
dc.citation.volume9en_US
dc.citation.issue8en_US
dc.citation.spageen_US
dc.citation.epageen_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
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