کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2201494 1100022 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Protein kinase G type-Iα phosphorylates the apoptosis-regulating protein Bad at serine 155 and protects against apoptosis in N1E-115 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Protein kinase G type-Iα phosphorylates the apoptosis-regulating protein Bad at serine 155 and protects against apoptosis in N1E-115 cells
چکیده انگلیسی

Previous studies from our laboratory have shown that the cGMP/protein kinase G (PKG) signaling pathway plays an essential role in preventing spontaneous apoptosis in neural cells; however, the mechanism is not understood. A potential downstream target of PKG is the apoptosis-regulating protein Bad, which contains a sequence around its serine 155 (ser155 in mouse Bad, equivalent to ser118 in human Bad) predicted to be a consensus motif for PKG-catalyzed phosphorylation. Using both in vitro and cell-based experiments, we determined if PKG phosphorylates Bad at ser155 and if blocking/stimulating PKG-catalyzed Bad phosphorylation causes pro-apoptotic/anti-apoptotic responses. Recombinant PKG type-Iα (PKG-Iα) was found to directly phosphorylate recombinant Bad at ser155 in vitro. In N1E-115 mouse neural cells, which naturally express PKG-Iα as the predominant PKG isoform, addition of 8-Br-cGMP (0.1–1.0 mM), a cell-permeable direct PKG-Iα activator, increased ser155 phosphorylation of Bad. ODQ (50 μM), a soluble guanylyl cyclase inhibitor that lowers cGMP/PKG activity, decreased serum-induced ser155 phosphorylation of Bad and induced apoptosis in N1E-115 cells. Treatment with DT-2 and DT-3, selective PKG-Iα inhibitors, both decreased Bad ser155 phosphorylation and induced apoptosis. The data indicate that PKG-Iα directly phosphorylates Bad at ser155, which may participate in cGMP/PKG-induced anti-apoptotic/cytoprotective effects in neural cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 56, Issue 4, March 2010, Pages 546–553
نویسندگان
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