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| J. Biol. Chem. Oct (2006); 281(42):31188-201 | |
| Nuclear export of S6K1 II is regulated by protein kinase CK2 phosphorylation at Ser-17- | |
| Panasyuk G, Nemazanyy I, Zhyvoloup A, Bretner M, Litchfield DW, Filonenko V, Gout IT | |
| Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03143, Ukraine- | |
| Abstract: Ribosomal S6 kinases -S6Ks- are principal players in the regulation of cell growth and energy metabolism- Signaling via phosphatidylinositol 3-kinase and mammalian target of rapamycin pathways mediates the activation of S6K in response to various mitogenic stimuli- The family of S6Ks consists of two forms, S6K1 and -2, that have cytoplasmic and nuclear splicing variants, S6K1 II and S6K1 I, respectively- Nuclear-cytoplasmic shuttling of both isoforms induced by mitogenic stimuli has been reported recently- Here we present the identification of protein kinase CK2 -CK2- as a novel binding and regulatory partner for S6K1 II- The interaction between S6K1 II and CK2beta regulatory subunit was initially identified in a yeast two-hybrid screen and further confirmed by co-immunoprecipitation of transiently expressed and endogenous proteins- The interaction between S6K1 II and CK2 was found to occur in serum-starved and serum-stimulated cells- In addition, we found that S6K1 II is a substrate for CK2- The localization of the CK2 phosphorylation site was narrowed down to Ser-17 in S6K1 II- Mutational analysis and the use of phosphospecific antibody indicate that Ser-17 is a major in vitro and in vivo phosphorylation site for CK2- Functional studies reveal that, in contrast to the wild type kinase, the phosphorylation-mimicking mutant of S6K1 II -S17E- retains its cytoplasmic localization in serum-stimulated cells- Treatment of cells with the nuclear export inhibitor leptomycin B revealed that the S17E mutant accumulates in the nucleus to the same extent as S6K1 II wild type- These results indicate that nuclear import of the S17E mutant is not affected, although the export is significantly enhanced- We also provide evidence that nuclear export of S6K1 is mediated by a CRM1-dependent mechanism- Taken together, this study establishes a functional link between S6K1 II and CK2 signaling, which involves the regulation of S6K1 II nuclear export by CK2-mediated phosphorylation of Ser-17- | |
| [PUBMED: 16895915] |   |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |