Publikation: Protein kinase PKR is required for platelet-derived growth factor signaling of c-fos gene expression via Erks and Stat3
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The double-stranded RNA (dsRNA)-activated protein kinase PKR is an interferon (IFN)-induced enzyme that controls protein synthesis through phosphorylation of eukaryotic initiation factor 2α (eIF-2α). PKR also regulates signals initiated by diverse stimuli, including dsRNA, IFN-γ, tumor necrosis factor-α, interleukin-1 and lipopolysaccharide, to different transcription factors, resulting in pro-inflammatory gene expression. Stat3 plays an essential role in promoting cell survival and proliferation by different growth factors, including platelet-derived growth factor (PDGF). Here we show that PKR physically interacts with Stat3 and is required for PDGF-induced phosphorylation of Stat3 at Tyr705 and Ser727, resulting in DNA binding and transcriptional activation. PKR-mediated phosphorylation of Stat3 on Ser727 is indirect and channeled through Erks. Although PKR is pre-associated with the PDGF β-receptor, treatment with PDGF only modestly activates PKR. However, the induction of c-fos by PDGF is defective in PKRnull cells. Taken together, these results establish PKR as an upstream regulator of activation of Stat3 and as a common mediator of both growth-promoting and growth-inhibitory signals.
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DEB, Amitabha, Maryam ZAMANIAN-DARYOUSH, Zan XU, Suzanne KADEREIT, Bryan R. G. WILLIAMS, 2001. Protein kinase PKR is required for platelet-derived growth factor signaling of c-fos gene expression via Erks and Stat3. In: EMBO Journal. 2001, 20(10), pp. 2487-2496. ISSN 0261-4189. eISSN 1460-2075. Available under: doi: 10.1093/emboj/20.10.2487BibTex
@article{Deb2001Prote-6757, year={2001}, doi={10.1093/emboj/20.10.2487}, title={Protein kinase PKR is required for platelet-derived growth factor signaling of c-fos gene expression via Erks and Stat3}, number={10}, volume={20}, issn={0261-4189}, journal={EMBO Journal}, pages={2487--2496}, author={Deb, Amitabha and Zamanian-Daryoush, Maryam and Xu, Zan and Kadereit, Suzanne and Williams, Bryan R. G.} }
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