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. 2018 Jun 22;8:9511. doi: 10.1038/s41598-018-27864-6

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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GRAMD1B plays a key role in the linkage between JAK/STAT and Akt signaling. (a) Effects of JAK/STAT signaling inhibition by AG490 on PI3K/Akt signaling. Note that AG490 dose-dependently increases p-Akt levels but does not affect p-PI3K levels, suggesting that JAK/STAT signaling acts downstream to PI3K but upstream/parallel to Akt. Full-length blots are included in Supplementary Fig. S10. (b) Effects of Akt signaling inhibition on JAK/STAT signaling. Note that p-STAT3 levels are not altered by MK-2206. Full-length blots are included in Supplementary Fig. S11. (c) GRAMD1B inhibition-induced p-Akt levels are further increased in the presence of AG490. Full-length blots are included in Supplementary Fig. S12. (d) Schematic for the mechanism of action of GRAMD1B, suggesting its pivotal role in the regulation of JAK/STAT and Akt signaling.