کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1934226 1050635 2008 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nck-1 interacts with PKR and modulates its activation by dsRNA
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Nck-1 interacts with PKR and modulates its activation by dsRNA
چکیده انگلیسی

Activation of the double-stranded RNA (dsRNA)-activated protein kinase PKR results in inhibition of general translation through phosphorylation of the eukaryotic initiation factor 2 alpha-subunit on serine 51 (eIF2αSer51). Previously, we have reported that the adaptor protein Nck-1 modulates eIF2αSer51 phosphorylation by a subset of eIF2α kinases, including PKR. Herein, we demonstrate that Nck-1 prevents efficient activation of PKR by dsRNA, revealing that Nck-1 acts at the level of PKR. In agreement, Nck-1 impairs p38MAPK activation and attenuates cell death induced by dsRNA, in addition to diminish eIF2αSer51 phosphorylation. Our data show that the inhibitory effect of Nck-1 on PKR is reversible, as it could be overcome by increasing levels of dsRNA. Interestingly, we found that Nck-1 interacts with the inactive form of PKR, independently of its Src homology domains. Furthermore, we uncovered that Nck-1 is substrate of PKR in vitro. All together, our data provide the first evidence identifying Nck-1 as a novel endogenous regulator of PKR and support the notion that Nck-1–PKR interaction could be a way to limit PKR activation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 377, Issue 1, 5 December 2008, Pages 231–235
نویسندگان
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