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http://purl.uniprot.org/citations/24308939http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Angiopoietin-1 (Ang-1) promotes survival and migration of endothelial cells, in part through the activation of mitogen-activated protein kinase (MAPK) pathways downstream of Tie-2 receptors. Dual-specificity phosphatases (DUSPs) dephosphorylate phosphotyrosine and phosphoserine/phosphothreonine residues on target MAPKs. The mechanisms by which DUSPs modulate MAPK activation in Ang-1/Tie-2 receptor signaling are unknown in endothelial cells.

Methods and results

Expression of various DUSPs in human umbilical vein endothelial cells exposed to Ang-1 was measured. The functional roles of DUSPs in Ang-1-induced regulation of MAPK activation, endothelial cell survival, migration, differentiation, and permeability were measured using selective siRNA oligos. Ang-1 differentially induces DUSP1, DUSP4, and DUSP5 in human umbilical vein endothelial cells through activation of the PI-3 kinase, ERK1/2, p38, and SAPK/JNK pathways. Lack-of-function siRNA screening revealed that DUSP1 preferentially dephosphorylates p38 protein and is involved in Ang-1-induced cell migration and differentiation. DUSP4 preferentially dephosphorylates ERK1/2, p38, and SAPK/JNK proteins and, under conditions of serum deprivation, is involved in Ang-1-induced cell migration, several antiapoptotic effects, and differentiation. DUSP5 preferentially dephosphorylates ERK1/2 proteins and is involved in cell survival and inhibition of permeability.

Conclusions

DUSP1, DUSP4, and DUSP5 differentially modulate MAPK signaling pathways downstream of Tie-2 receptors, thus highlighting the importance of these phosphatases to Ang-1-induced angiogenesis."xsd:string
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http://purl.uniprot.org/citations/24308939http://purl.uniprot.org/core/author"Hussain S.N."xsd:string
http://purl.uniprot.org/citations/24308939http://purl.uniprot.org/core/author"Echavarria R."xsd:string
http://purl.uniprot.org/citations/24308939http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24308939http://purl.uniprot.org/core/name"J Am Heart Assoc"xsd:string
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http://purl.uniprot.org/citations/24308939http://purl.uniprot.org/core/title"Regulation of angiopoietin-1/Tie-2 receptor signaling in endothelial cells by dual-specificity phosphatases 1, 4, and 5."xsd:string
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