Phosphorylation of STAT-3 in Response to Basic Fibroblast Growth Factor Occurs through a Mechanism Involving Platelet-activating Factor, JAK-2, and Src in Human Umbilical Vein Endothelial Cells

摘要: Platelet-activating factor (PAF) is a potent proinflammatory phospholipid with multiple pathological and physiological effects. We have shown that basic fibroblast growth (bFGF) supplementation induces rapid proliferation of human umbilical vein endothelial cells (HUVEC), which reduced upon removal bFGF or by immunoneutralization. The PAF receptor antagonist LAU-8080 inhibited bFGF-stimulated HUVEC proliferation, indicating the involvement in bFGF-mediated signaling HUVEC. Although FGF phosphorylation was not affected LAU-8080, prolonged phosphorylation, activation Erk-1 -2 were attenuated. Phosphorylation STAT-3 observed presence bFGF, attenuated PAFR antagonists. PAF-induced pretreated either Src inhibitor PP1 JAK-2 AG-490 indicated (i) immediate (1 min) dependent on Src, (ii) JAK-2-dependent occurs after delayed (30 exposure, (iii) (60 may be through and/or JAK-2. Attenuation antagonists receptor. Taken together, these findings suggest production important for dual kinase mechanism involved PAF-mediated signal transduction cascade.