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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Abe MK, Kuo W-L, Hershenson MB and Rosner MR . 1999 Mol Cell Biol 19: 1301–1312
Baichwal VR and Baeuerle PA . 1997 Curr Biol 7: 94–96
Baldwin Jr AS . 1996 Annu Rev Immunol 14: 649–681
Baniahmad A, Kohne AC and Renkawitz R . 1992 EMBO J 11: 1015–1023
Beg AA, Finco TS, Nantermet PV and Baldwin Jr AS . 1993 Mol Cell Biol 13: 3301–3310
Berthelsen J, Zappavigna V, Mavilio F and Blasi F . 1998 EMBO J 17: 1423–1433
Bird TA, Schooley K, Dower SK, Hagen H and Virca GD . 1997 J Biol Chem 272: 32606–32612
Boehmelt G, Madruga J, Dorfler P, Briegel K, Schwartz H, Enrietto PJ and Zenke M . 1995 Cell 80: 341–352
Boulton TG, Nye SH, Robbins DJ, Ip NY, Radziejewska E, Morgenbesser SD, DePinho RA, Panayotatos N, Cobb MH and Yancopoulos GD . 1991 Cell 65: 663–675
Boyle WJ, Smeal T, Defize LHK, Angel P, Woodgett JR, Karin M and Hunter T . 1991 Cell 64: 573–584
Bull P, Morley KL, Hoekstra MF, Hunter T and Verma IM . 1990 Mol Cell Biol 10: 5473–5485
Carrasco D, Risso CA, Dorfman K and Bravo R . 1996 EMBO J 15: 3640–3650
Chen C, Agnès F and Gélinas C . 1999 Mol Cell Biol 19: 307–316
Chen ZJ, Hagler J, Palombella VJ, Melandri F, Scherer D, Ballard D and Maniatis T . 1995 Genes Dev 9: 1586–1597
Chen ZJ, Parent L and Maniatis T . 1996 Cell 84: 853–862
Cheng M, Boulton TG and Cobb MH . 1996 J Biol Chem 271: 8951–8958
Drier EA, Huang LH and Steward R . 1999 Genes Dev 13: 556–568
Druker BJ, Neumann M, Okuda K, Franza BRJ and Griffin JD . 1994 J Biol Chem 269: 5387–5390
Hansen SK, Baeuerle PA and Blasi F . 1994 Mol Cell Biol 14: 2593–2603
Hayashi T, Sekine T and Okamoto T . 1993 J Bio Chem 268: 26790–26795
Henkel T, Machleidt T, Alkalay I, Kronke M, Ben-Neriah Y and Baeuerle PA . 1993 Nature 365: 182–185
Hunter T and Karin M . 1992 Cell 70: 375–387
Jacobs D, Glossip D, Xing H, Muslin AJ and Kornfeld K . 1999 Genes Dev 13: 163–175
Kaelin WGJ, Pallas DC, DeCaprio JA, Kaye FJ and Livingston DM . 1991 Cell 64: 521–532
Karin M . 1994 Curr Opin Cell Biol 6: 415–424
Karin M . 1995 J Biol Chem 270: 16483–16486
Kerr LD, Ransone LJ, Wamsley P, Schmitt MJ, Boyer TG, Zhou Q, Berk AJ and Verma IM . 1993 Nature 365: 412–419
Knoepfler PS and Kamps MP . 1995 Mol Cell Biol 15: 5811–5819
Kopp E and Ghosh S . 1995 Adv Immunol 58: 1–27
Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bachinger HP, Brennan RG, Roberts SG, Green MR and Goodman RH . 1994 Nature 370: 223–226
Leppa A, Saffrich R, Ansorge W and Bohmann D . 1998 EMBO J 15: 4404–4413
Lewis RB, McClure J, Rup B, Niesel DW, Garry RF, Hoelzer JD, Nazerian K and Bose Jr HR . 1981 Cell 25: 421–431
Luque I and Gélina C . 1997 Semin Cancer Biol 8: 103–111
Mosialos G, Hamer P, Capobianco AJ, Laursen RA and Gilmore TD . 1991 Mol Cell Biol 11: 5867–5877
Naumann M and Scheidereit C . 1994 EMBO J 13: 4597–4607
Palombella VJ, Rando OJ, Goldberg AL and Maniatis T . 1994 Cell 78: 773–785
Pellicioli A, Lucca C, Liberi G, Marini F, Lopes M, Plevani P, Romano A, Di Fiore PP and Foiani M . 1999 EMBO J 18: 6561–6572
Resnati M, Guttinger M, Valcamonica S, Sidenius N, Blasi F and Fazioli F . 1996 EMBO J 15: 1572–1582
Rice NR and Ernst MK . 1993 EMBO J 12: 4685–4695
Sambrook J, Fritsch EF and Maniatis T . 1989 Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York
Sassone-Corsi P . 1995 Annu Rev Cell Dev Biol 11: 355–377
Schmitz ML and Baeuerle PA . 1991 EMBO J 10: 3805–3817
Smith DB and Johnson KS . 1988 Gene 67: 31–40
Verma IM and Stevenson J . 1997 Proc Natl Acad Sci USA 94: 11758–11760
Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D and Miyamoto S . 1995 Genes Dev 9: 2723–2735
Xu X, Prorock C, Ishikawa H, Maldonado E, Ito Y and Gélinas C . 1993 Mol Cell Biol 13: 6733–6741
Zappavigna V, Sartori D and Mavilio F . 1994 Genes Dev 8: 732–744
Zhong H, Su Yang H, Erdjument-Bromage H, Tempst P and Ghosh S . 1997 Cell 89: 413–424
Zhong H, Voll R and Ghosh S . 1998 Mol Cell 1: 661–671
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).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203543
Keywords
This article is cited by
-
Regulation of B-cell function by NF-kappaB c-Rel in health and disease
Cellular and Molecular Life Sciences (2020)
-
Mutation of an IKK phosphorylation site within the transactivation domain of REL in two patients with B-cell lymphoma enhances REL's in vitro transforming activity
Oncogene (2007)
-
Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway
Oncogene (2006)
-
IKKα limits macrophage NF-κB activation and contributes to the resolution of inflammation
Nature (2005)