Abstract
The VRK1 kinase is a novel Ser-Thr kinase in the human kinome that diverged from the casein kinase 1 branch. These kinases phosphorylate transcription factors related to stress responses, such as p53. In this report we have studied the phosphorylation of the transcription factor c-Jun in its N-terminal region. The VRK1 protein phosphorylates c-Jun with a Km of 0.4 μ M, and is not inhibited by SP600125. VRK1 phosphorylates c-Jun in Ser63 and Ser73 in vitro, the same residues targeted by the N-terminal kinase of c-Jun (JNK). This phosphorylation induces the stabilization and accumulation of the c-Jun protein. VRK1 phosphorylates the endogenous c-Jun in Ser63. VRK1 activates c-Jun dependent transcription, which is dependent on phosphorylation of Ser63 and Ser73. The c-Jun with Ser63Ala and Ser73Ala substitutions is not transcriptionally active when cotransfected with VRK1. VRK1 interacts with c-Jun but not with JNK. The cotransfection of VRK1 and JNK has an additive effect on the transcriptional activation of c-Jun indicating that they can cooperate when both are at suboptimal dose; otherwise, maximum effect by one of them prevents the effect of the other. The VRK1-c-Jun connection represents a component of a new signaling pathway whose upstream elements remain to be identified.
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References
Adler V, Fuchs SY, Kim J, Kraft A, King MP, Pelling J and Ronai Z . (1995). Cell Growth Differ., 6, 1437–1446.
Antonyak MA, Kenyon LC, Godwin AK, James DC, Emlet DR, Okamoto I, Tnani M, Holgado-Madruga M, Moscatello DK and Wong AJ . (2002). Oncogene, 21, 5038–5046.
Aoyagi K, Shima I, Wang M, Hu Y, Garcia FU and Stearns ME . (1998). Clin. Cancer Res., 4, 2153–2160.
Barcia R, Lopez-Borges S, Vega FM and Lazo PA . (2002). Arch. Biochem. Biophys., 399, 1–5.
Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM and Anderson DW . (2001). Proc. Natl. Acad. Sci. USA, 98, 13681–13686.
Chang L and Karin M . (2001). Nature, 410, 37–40.
Clerk A and Sugden PH . (1997). Biochem. J., 325, 801–810.
Davis RJ . (2000). Cell, 103, 239–252.
Dlakic M, Grinberg AV, Leonard DA and Kerppola TK . (2001). EMBO J., 20, 828–840.
Dong C, Yang DD, Tournier C, Whitmarsh AJ, Xu J, Davis RJ and Flavell RA . (2000). Nature, 405, 91–94.
Dunn C, Wiltshire C, MacLaren A and Gillespie DA . (2002). Cell. Signal., 14, 585–593.
Eferl R and Wagner EF . (2003). Nat. Rev. Cancer, 3, 859–868.
Fuchs SY, Tappin I and Ronai Z . (2000). J. Biol. Chem., 275, 12560–12564.
Hai T and Hartman MG . (2001). Gene, 273, 1–11.
Hall MC, Young DA, Waters JG, Rowan AD, Chantry A, Edwards DR and Clark IM . (2003). J. Biol. Chem., 278, 10304–10313.
Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM and Firestein GS . (2001). J. Clin. Invest., 108, 73–81.
Hernandez-Torres J, Yunta M and Lazo PA . (2001). J. Biol. Chem., 276, 35405–35413.
Kennedy NJ and Davis RJ . (2003). Cell Cycle, 2, 199–201.
Kerppola TK and Curran T . (1993). Mol. Cell. Biol., 13, 5479–5489.
Leppa S and Bohmann D . (1999). Oncogene, 18, 6158–6162.
Lopez-Borges S and Lazo PA . (2000). Oncogene, 19, 3656–3664.
Manning G, Whyte DB, Martinez R, Hunter T and Sudarsanam S . (2002). Science, 298, 1912–1934.
Meggiato T, Calabrese F, De Cesare CM, Baliello E, Valente M and Del Favero G . (2003). Pancreas, 26, 65–70.
Neyns B, Katesuwanasing Vermeij J, Bourgain C, Vandamme B, Amfo K, Lissens W, DeSutter P, Hooghe-Peters E and DeGreve J . (1996). Oncogene, 12, 1247–1257.
Nezu J, Oku A, Jones MH and Shimane M . (1997). Genomics, 45, 327–331.
Nichols RJ and Traktman P. . (2004). J. Biol. Chem., 279, 7934–7946.
Sevilla A, Santos CR, Vega FM and Lazo PA . (2004). J. Biol. Chem., 279, 27458–27465.
Shaulian E and Karin M . (2001). Oncogene, 20, 2390–2400.
Shaulian E and Karin M . (2002). Nat. Cell. Biol., 4, E131–E136.
Shuman JD, Cheong J and Coligan JE . (1997). J. Biol. Chem., 272, 12793–12800.
Szabo E, Riffe ME, Steinberg SM, Birrer MJ and Linnoila RI . (1996). Cancer Res., 56, 305–315.
Tiniakos DG, Mellon K, Anderson JJ, Robinson MC, Neal DE and Horne CH . (1994). Br. J. Urol., 74, 757–761.
van Dam H and Castellazzi M . (2001). Oncogene, 20, 2453–2464.
Vega FM, Gonzalo P, Gaspar ML and Lazo PA . (2003). FEBS Lett., 544, 176–180.
Volm M, Koomagi R, Mattern J and Efferth T . (2002). Clin. Cancer Res., 8, 1843–1848.
Weiss L, Whitmarsh AJ, Yang DD, Rincon M, Davis RJ and Flavell RA . (2000). J. Exp. Med., 191, 139–146.
Wodrich W and Volm M . (1993). Carcinogenesis, 14, 1121–1124.
Yunta M, Oliva JL, Barcia R, Horejsi V, Angelisova P and Lazo PA . (2002). Eur. J. Biochem., 269, 1012–1021.
Acknowledgements
AS and CS have predoctoral fellowships from Consejo Superior de Investigaciones Científicas and the Fundação para a Ciência e a Tecnologia (Portugal) respectively. This work was funded by grants from Ministerio de Educación y Ciencia (SAF2000-0169, SAF2004-2900), Fondo de Investigación Sanitaria (FIS02/0585), Junta de Castilla y León-Consejerías de Educación (CSI18-03) and Sanidad (SA 01/02), Fundación de Investigación Médica MMA and Fundación Memoria Samuel Solórzano Barruso.
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Sevilla, A., Santos, C., Barcia, R. et al. c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK). Oncogene 23, 8950–8958 (2004). https://doi.org/10.1038/sj.onc.1208015
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DOI: https://doi.org/10.1038/sj.onc.1208015
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