کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2789286 1154489 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Suppression of Protein Phosphatase 2 Differentially Modulates VEGF- and FGF2-Induced Signaling in Ovine Fetoplacental Artery Endothelial Cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
Suppression of Protein Phosphatase 2 Differentially Modulates VEGF- and FGF2-Induced Signaling in Ovine Fetoplacental Artery Endothelial Cells
چکیده انگلیسی

Vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) elicit cellular responses via activation of protein kinases and phosphatases. We have reported that the MEK1/2/ERK1/2 and PI3K/AKT1 pathways are critical for VEGF- and FGF2-stimulated ovine fetoplacental artery endothelial (OFPAE) cell proliferation. We have also shown that protein phosphatase 3 (PPP3) differentially modulates VEGF- and FGF2-stimulated cell proliferation and activation of ERK1/2 and AKT1 in OFPAE cells. Herein, we investigated if protein phosphatase 2 (PPP2) modulated VEGF- and FGF2-induced ERK1/2, AKT1, and p38 MAPK activation and VEGF- and FGF2-stimulated cell proliferation in OFPAE cells. Small interfering RNA (siRNA) specifically targeting human PPP2CA catalytic subunit α (PPP2CA) was used to suppress PPP2CA expression in OFPAE cells. When compared with scrambled siRNA, PPP2CA siRNA decreased (p < 0.05) PPP2CA protein levels (∼70%) and activity (∼50%) without altering protein levels of PPP3 catalytic subunit α (PPP3CA), nitric oxide synthase 3 (NOS3), ERK1/2, AKT1, and p38 MAPK. FGF2, but not VEGF rapidly (≤5 min) induced p38 MAPK phosphorylation. Suppression of PPP2CA enhanced (p < 0.05) VEGF-induced AKT1, but not ERK1/2 phosphorylation, whereas inhibited (p < 0.05) FGF2-induced ERK1/2 and p38 MAPK and slightly attenuated FGF2-induced AKT1 phosphorylation. Suppression of PPP2CA did not significantly affect VEGF- and FGF2-stimulated OFPAE cell proliferation. Thus, suppression of PPP2CA alone differentially modulated VEGF- and FGF2-induced ERK1/2, AKT1, and p38 MAPK activation, without altering VEGF- and FGF2-stimulated cell proliferation in OFPAE cells. These data also suggest that signaling molecules other than ERK1/2, AKT1, and p38 MAPK are important mediators for VEGF- and FGF2-stimulated OFPAE cell proliferation after PPP2CA suppression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Placenta - Volume 30, Issue 10, October 2009, Pages 907–913
نویسندگان
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