| http://purl.uniprot.org/citations/21536681 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21536681 | http://www.w3.org/2000/01/rdf-schema#comment | "In view of understanding the mechanisms of retinal neovascularization, we had reported previously that vascular endothelial growth factor (VEGF)-induced pathological retinal angiogenesis requires the activation of Src-PLD1-PKCγ signaling. In the present work, we have identified cytosolic phospholipase A(2) (cPLA(2)) as an effector molecule of Src-PLD1-PKCγ signaling in the mediation of VEGF-induced pathological retinal angiogenesis based on the following observations. VEGF induced cPLA(2) phosphorylation in a time-dependent manner in human retinal microvascular endothelial cells (HRMVECs). VEGF also induced arachidonic acid (AA) release in a dose-, time-, and cPLA(2)-dependent manner. Depletion of cPLA(2) levels inhibited VEGF-induced HRMVEC DNA synthesis, migration, and tube formation. In addition, the exogenous addition of AA rescued VEGF-induced HRMVEC DNA synthesis, migration, and tube formation from inhibition by down-regulation of cPLA(2). Inhibition of Src, PLD1, or PKCγ attenuated VEGF-induced cPLA(2) phosphorylation and AA release. Consistent with these findings, hypoxia induced cPLA(2) phosphorylation and activity in VEGF-Src-PLD1-PKCγ-dependent manner in a mouse model of oxygen-induced retinopathy. In addition, siRNA-mediated down-regulation of cPLA(2) levels in the retina abrogated hypoxia-induced retinal endothelial cell proliferation and neovascularization. These observations suggest that cPLA(2)-dependent AA release is required for VEGF-induced Src-PLD1-PKCγ-mediated pathological retinal angiogenesis."xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m110.217786"xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/author | "Wang D."xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/author | "Zhang Q."xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/author | "Singh N.K."xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/author | "Rao G.N."xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/author | "Gadiparthi L."xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/author | "Rao C.h.M."xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/author | "Kundumani-Sridharan V."xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/pages | "22489-22498"xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/title | "Activation of cytosolic phospholipase A2 downstream of the Src-phospholipase D1 (PLD1)-protein kinase C gamma (PKCgamma) signaling axis is required for hypoxia-induced pathological retinal angiogenesis."xsd:string |
| http://purl.uniprot.org/citations/21536681 | http://purl.uniprot.org/core/volume | "286"xsd:string |
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