Abstract 1064: Pim serine/threonine kinases regulate the phosphorylation and function of eIF4B protein

Abstract

Abstract Eukaryotic initiation factor 4B (eIF4B) is a multidomain protein with a critical role in the initiation of protein synthesis, and has long been known as a hyperphosphorylated protein. It has been thought that function of eIF4B can be regulated by phosphorylation. The Pim family of Ser/Thr kinase, which is consisted of three members: Pim-1, Pim-2, and Pim-3, has been implicated in multiple cellular processes including cellular survival, anti-apoptosis and tumorigenesis. In this study, we identified eIF4B as a Pim kinase substrate. We found that Pim-1, Pim-2 but not Pim-3 can upregulate phosphorylation levels of eIF4B on Ser406 and Ser422 using 293T cell system, while kinase-dead mutants of Pim-1 or Pim-2 significantly inhibit phosphorylation of eIF4B. Furthermore, in vitro kinase assay revealed that Pim-1 kinase can directly phosphorylate eIF4B on Ser422. As expected, we found that Pim-1 kinase directly bound to eIF4B using GST-pull down assay and co-immunoprecipitation experiments. Interestingly, levels of eIF4B protein in v-Abl transformants treated with the Abl kinase inhibitor imatinib decreased markedly, indicating that expression of eIF4B is Abl kinase dependant. Our results suggest that Pim kinases regulate cellular processes via phosphorylating downstream eIF4B, and thereby alter the function of eIF4B in v-Abl transformants. Together, these data possibly provide new insights into molecular mechanisms of Abl oncogene-mediated cellular transformation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1064. doi:10.1158/1538-7445.AM2011-1064