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cRel-TD kinase: a serine/threonine kinase binding in vivo and in vitro c-Rel and phosphorylating its transactivation domain

Abstract

The activity of transcription factors is often modulated by signal responsive protein kinases. Rel/NF-κB transcription factors are regulated by IκB inhibitors, the phosphorylation of which causes ubiquitination and degradation, resulting in nuclear translocation of NF-κB and activation of target genes. Here we report pull-down and immunoprecipitation experiments showing that a mammalian 66 kDa protein kinase binds murine c-Rel, both in vitro and in vivo. This kinase appears to have at least two binding sites on c-Rel, a proline-directed serine/threonine substrate specificity similar to MAP kinases and to specifically phosphorylate the C-terminal domain of murine c-Rel at an ERK consensus site.

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Acknowledgements

The authors wish to thank V Zappavigna (H-S Raffaele, Milan-Italy) for the generous gift of pTUAS plasmid and G Haegemann (Gent, Belgium) for the pABGal4-RelA plasmid. We are also grateful to Simon Plyte (Pharmacia & UpJohn, Milan-Italy) for critical reading of the manuscript and helpful suggestions. We are grateful to PP Di Fiore (E.I.O., Milan-Italy) for stimulating discussion. This work was supported by grants from AIRC (Associazione Italiana per la Ricerca sul Cancro) and EU (contract number BMH4-CT97-2453).

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Fognani, C., Rondi, R., Romano, A. et al. cRel-TD kinase: a serine/threonine kinase binding in vivo and in vitro c-Rel and phosphorylating its transactivation domain. Oncogene 19, 2224–2232 (2000). https://doi.org/10.1038/sj.onc.1203543

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