Archives of Pharmacal Research

, Volume 40, Issue 3, pp 291–303 | Cite as

RSK2 and its binding partners in cell proliferation, transformation and cancer development

  • Yong-Yeon ChoEmail author


RSK2 is a serine/threonine kinase and a member of the p90 ribosomal S6 kinase (p90RSK; RSKs) family, which regulates cell proliferation and transformation induced by tumor promoters such as epithelial growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate (TPA), and ultraviolet (UV) radiation. RSKs respond to many growth factors, hormones, neurotransmitters and environmental stresses. In signaling cascades, RSK2 is regulated under the control of extracellular signal-regulated kinase 1 (ERK1) and 2 (ERK2) activities and is positioned upstream of transcription and epigenetic factors involved in cell proliferation, cell transformation and cancer development, as well as some kinases that modulate cell cycle progression. Over the last decade, our research group has studied the etiological roles of RSK2 in human cancer development, discovering that RSK2 plays a key role in cell proliferation, transformation and cancer development in humans. Based on our research, we concluded that RSK2 plays a key role as an onco-kinase by combinational protein–protein interaction with different binding partners depending on the cellular context. In this review, we discuss the function of the RSK2 signaling axis by interactions with binding partners in cancer development.


RSK2 Protein–protein interaction Signaling axis Cell proliferation Cell transformation 



This work was supported in part by the Research Fund of The Catholic University of Korea (M-2016-B0002-00027), by the Ministry of Science, ICT and Future Planning (NRF-2012M3A9B6055466 and -2014R1A211050004).

Compliance with ethical standards

Conflict of interest

The authors declares that there is no conflict of interest.


  1. Arul N, Cho YY (2013) A rising cancer prevention target of RSK2 in human skin cancer. Front Oncol 3:201CrossRefPubMedPubMedCentralGoogle Scholar
  2. Baksh S, Widlund HR, Frazer-Abel AA, Du J, Fosmire S, Fisher DE, DeCaprio JA, Modiano JF, Burakoff SJ (2002) NFATc2-mediated repression of cyclin-dependent kinase 4 expression. Mol Cell 10:1071–1081CrossRefPubMedGoogle Scholar
  3. Bassing CH, Suh H, Ferguson DO, Chua KF, Manis J, Eckersdorff M, Gleason M, Bronson R, Lee C, Alt FW (2003) Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 114:359–370CrossRefPubMedGoogle Scholar
  4. Bhatt RR, Ferrell JE Jr (1999) The protein kinase p90 rsk as an essential mediator of cytostatic factor activity. Science 286:1362–1365CrossRefPubMedGoogle Scholar
  5. Blenis J (1993) Signal transduction via the MAP kinases: proceed at your own RSK. Proc Natl Acad Sci USA 90:5889–5892CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bode AM, Dong Z (2003) Mitogen-activated protein kinase activation in UV-induced signal transduction. Sci STKE 2003:RE2PubMedGoogle Scholar
  7. Boldin MP, Goncharov TM, Goltsev YV, Wallach D (1996) Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 85:803–815CrossRefPubMedGoogle Scholar
  8. Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME (1999) Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 286:1358–1362CrossRefPubMedGoogle Scholar
  9. Booher RN, Holman PS, Fattaey A (1997) Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity. J Biol Chem 272:22300–22306CrossRefPubMedGoogle Scholar
  10. Bowden GT (2004) Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling. Nat Rev Cancer 4:23–35CrossRefPubMedGoogle Scholar
  11. Brown JR, Nigh E, Lee RJ, Ye H, Thompson MA, Saudou F, Pestell RG, Greenberg ME (1998) Fos family members induce cell cycle entry by activating cyclin D1. Mol Cell Biol 18:5609–5619CrossRefPubMedPubMedCentralGoogle Scholar
  12. Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 276:42462–42467CrossRefPubMedGoogle Scholar
  13. Bushdid PB, Osinska H, Waclaw RR, Molkentin JD, Yutzey KE (2003) NFATc3 and NFATc4 are required for cardiac development and mitochondrial function. Circ Res 92:1305–1313CrossRefPubMedGoogle Scholar
  14. Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, Reina-San-Martin B, Coppola V, Meffre E, Difilippantonio MJ, Redon C, Pilch DR, Olaru A, Eckhaus M, Camerini-Otero RD, Tessarollo L, Livak F, Manova K, Bonner WM, Nussenzweig MC, Nussenzweig A (2002) Genomic instability in mice lacking histone H2AX. Science 296:922–927CrossRefPubMedPubMedCentralGoogle Scholar
  15. Celeste A, Difilippantonio S, Difilippantonio MJ, Fernandez-Capetillo O, Pilch DR, Sedelnikova OA, Eckhaus M, Ried T, Bonner WM, Nussenzweig A (2003) H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 114:371–383CrossRefPubMedPubMedCentralGoogle Scholar
  16. Chan DW, Chen BP, Prithivirajsingh S, Kurimasa A, Story MD, Qin J, Chen DJ (2002) Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev 16:2333–2338CrossRefPubMedPubMedCentralGoogle Scholar
  17. Chandrasekar B, Patel DN, Mummidi S, Kim JW, Clark RA, Valente AJ (2008) Interleukin-18 suppresses adiponectin expression in 3T3-L1 adipocytes via a novel signal transduction pathway involving ERK1/2-dependent NFATc4 phosphorylation. J Biol Chem 283:4200–4209CrossRefPubMedGoogle Scholar
  18. Cheung P, Allis CD, Sassone-Corsi P (2000) Signaling to chromatin through histone modifications. Cell 103:263–271CrossRefPubMedGoogle Scholar
  19. Cho YY, He Z, Zhang Y, Choi HS, Zhu F, Choi BY, Kang BS, Ma WY, Bode AM, Dong Z (2005) The p53 protein is a novel substrate of ribosomal S6 kinase 2 and a critical intermediary for ribosomal S6 kinase 2 and histone H3 interaction. Cancer Res 65:3596–3603CrossRefPubMedGoogle Scholar
  20. Cho YY, Yao K, Bode AM, Bergen HR 3rd, Madden BJ, Oh SM, Ermakova S, Kang BS, Choi HS, Shim JH, Dong Z (2007a) RSK2 mediates muscle cell differentiation through regulation of NFAT3. J Biol Chem 282:8380–8392CrossRefPubMedPubMedCentralGoogle Scholar
  21. Cho YY, Yao K, Kim HG, Kang BS, Zheng D, Bode AM, Dong Z (2007b) Ribosomal S6 kinase 2 is a key regulator in tumor promoter induced cell transformation. Cancer Res 67:8104–8112CrossRefPubMedPubMedCentralGoogle Scholar
  22. Cho YY, Yao K, Pugliese A, Malakhova ML, Bode AM, Dong Z (2009) A regulatory mechanism for RSK2 NH(2)-terminal kinase activity. Cancer Res 69:4398–4406CrossRefPubMedPubMedCentralGoogle Scholar
  23. Cho YY, Lee MH, Lee CJ, Yao K, Lee HS, Bode AM, Dong Z (2012) RSK2 as a key regulator in human skin cancer. Carcinogenesis 33:2529–2537CrossRefPubMedPubMedCentralGoogle Scholar
  24. Chow CW, Rincon M, Cavanagh J, Dickens M, Davis RJ (1997) Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway. Science 278:1638–1641CrossRefPubMedGoogle Scholar
  25. Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365:855–859CrossRefPubMedGoogle Scholar
  26. Cullen PJ, Lockyer PJ (2002) Integration of calcium and Ras signalling. Nat Rev Mol Cell Biol 3:339–348CrossRefPubMedGoogle Scholar
  27. David JP, Mehic D, Bakiri L, Schilling AF, Mandic V, Priemel M, Idarraga MH, Reschke MO, Hoffmann O, Amling M, Wagner EF (2005) Essential role of RSK2 in c-Fos-dependent osteosarcoma development. J Clin Invest 115:664–672CrossRefPubMedPubMedCentralGoogle Scholar
  28. De Cesare D, Jacquot S, Hanauer A, Sassone-Corsi P (1998) Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene. Proc Natl Acad Sci USA 95:12202–12207CrossRefPubMedPubMedCentralGoogle Scholar
  29. Dolcet X, Llobet D, Pallares J, Matias-Guiu X (2005) NF-kB in development and progression of human cancer. Virchows Arch 446:475–482CrossRefPubMedGoogle Scholar
  30. Dufresne SD, Bjorbaek C, El-Haschimi K, Zhao Y, Aschenbach WG, Moller DE, Goodyear LJ (2001) Altered extracellular signal-regulated kinase signaling and glycogen metabolism in skeletal muscle from p90 ribosomal S6 kinase 2 knockout mice. Mol Cell Biol 21:81–87CrossRefPubMedPubMedCentralGoogle Scholar
  31. Fernandez-Capetillo O, Lee A, Nussenzweig M, Nussenzweig A (2004) H2AX: the histone guardian of the genome. DNA Repair (Amst) 3:959–967CrossRefGoogle Scholar
  32. Frodin M, Jensen CJ, Merienne K, Gammeltoft S (2000) A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1. EMBO J 19:2924–2934CrossRefPubMedPubMedCentralGoogle Scholar
  33. Gavin AC, Ni Ainle A, Chierici E, Jones M, Nebreda AR (1999) A p90(rsk) mutant constitutively interacting with MAP kinase uncouples MAP kinase from p34(cdc2)/cyclin B activation in Xenopus oocytes. Mol Biol Cell 10:2971–2986CrossRefPubMedPubMedCentralGoogle Scholar
  34. Graef IA, Chen F, Chen L, Kuo A, Crabtree GR (2001) Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature. Cell 105:863–875CrossRefPubMedGoogle Scholar
  35. Graef IA, Wang F, Charron F, Chen L, Neilson J, Tessier-Lavigne M, Crabtree GR (2003) Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons. Cell 113:657–670CrossRefPubMedGoogle Scholar
  36. Grimes CA, Jope RS (2001) The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol 65:391–426CrossRefPubMedGoogle Scholar
  37. Gross SD, Schwab MS, Lewellyn AL, Maller JL (1999) Induction of metaphase arrest in cleaving Xenopus embryos by the protein kinase p90Rsk. Science 286:1365–1367CrossRefPubMedGoogle Scholar
  38. Gulati P, Markova B, Gottlicher M, Bohmer FD, Herrlich PA (2004) UVA inactivates protein tyrosine phosphatases by calpain-mediated degradation. EMBO Rep 5:812–817CrossRefPubMedPubMedCentralGoogle Scholar
  39. Gupta P, Prywes R (2002) ATF1 phosphorylation by the ERK MAPK pathway is required for epidermal growth factor-induced c-jun expression. J Biol Chem 277:50550–50556CrossRefPubMedGoogle Scholar
  40. Hailemariam K, Iwasaki K, Huang BW, Sakamoto K, Tsuji Y (2010) Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress. J Cell Sci 123:3863–3871CrossRefPubMedPubMedCentralGoogle Scholar
  41. Harum KH, Alemi L, Johnston MV (2001) Cognitive impairment in Coffin-Lowry syndrome correlates with reduced RSK2 activation. Neurology 56:207–214CrossRefPubMedGoogle Scholar
  42. Hazzalin CA, Mahadevan LC (2002) MAPK-regulated transcription: a continuously variable gene switch? Nat Rev Mol Cell Biol 3:30–40CrossRefPubMedGoogle Scholar
  43. Hernandez GL, Volpert OV, Iniguez MA, Lorenzo E, Martinez-Martinez S, Grau R, Fresno M, Redondo JM (2001) Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2. J Exp Med 193:607–620CrossRefPubMedPubMedCentralGoogle Scholar
  44. Hubbard SR, Miller WT (2007) Receptor tyrosine kinases: mechanisms of activation and signaling. Curr Opin Cell Biol 19:117–123CrossRefPubMedPubMedCentralGoogle Scholar
  45. Ichida M, Finkel T (2001) Ras regulates NFAT3 activity in cardiac myocytes. J Biol Chem 276:3524–3530CrossRefPubMedGoogle Scholar
  46. Impey S, McCorkle SR, Cha-Molstad H, Dwyer JM, Yochum GS, Boss JM, McWeeney S, Dunn JJ, Mandel G, Goodman RH (2004) Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell 119:1041–1054PubMedGoogle Scholar
  47. Jean D, Tellez C, Huang S, Davis DW, Bruns CJ, McConkey DJ, Hinrichs SH, Bar-Eli M (2000) Inhibition of tumor growth and metastasis of human melanoma by intracellular anti-ATF-1 single chain Fv fragment. Oncogene 19:2721–2730CrossRefPubMedGoogle Scholar
  48. Jin P, Gu Y, Morgan DO (1996) Role of inhibitory CDC2 phosphorylation in radiation-induced G2 arrest in human cells. J Cell Biol 134:963–970CrossRefPubMedGoogle Scholar
  49. Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 18:621–663CrossRefPubMedGoogle Scholar
  50. Kegley KM, Gephart J, Warren GL, Pavlath GK (2001) Altered primary myogenesis in NFATC3(-/-) mice leads to decreased muscle size in the adult. Dev Biol 232:115–126CrossRefPubMedGoogle Scholar
  51. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705CrossRefPubMedGoogle Scholar
  52. Kovary K, Bravo R (1991) The jun and fos protein families are both required for cell cycle progression in fibroblasts. Mol Cell Biol 11:4466–4472CrossRefPubMedPubMedCentralGoogle Scholar
  53. Lau AT, Lee SY, Xu YM, Zheng D, Cho YY, Zhu F, Kim HG, Li SQ, Zhang Z, Bode AM, Dong Z (2011) Phosphorylation of histone H2B serine 32 is linked to cell transformation. J Biol Chem 286:26628–26637CrossRefPubMedPubMedCentralGoogle Scholar
  54. Lee CJ, Lee MH, Lee JY, Song JH, Lee HS, Cho YY (2013) RSK2-induced stress tolerance enhances cell survival signals mediated by inhibition of GSK3beta activity. Biochem Biophys Res Commun 440:112–118CrossRefPubMedGoogle Scholar
  55. Lee CJ, Lee HS, Ryu HW, Lee MH, Lee JY, Li Y, Dong Z, Lee HK, Oh SR, Cho YY (2014) Targeting of magnolin on ERKs inhibits Ras/ERKs/RSK2-signaling-mediated neoplastic cell transformation. Carcinogenesis 35:432–441CrossRefPubMedGoogle Scholar
  56. Lee CJ, Jang JH, Lee JY, Lee MH, Li Y, Ryu HW, Choi KI, Dong Z, Lee HS, Oh SR, Surh YJ, Cho YY (2015a) Aschantin targeting on the kinase domain of mammalian target of rapamycin suppresses epidermal growth factor-induced neoplastic cell transformation. Carcinogenesis 36:1223–1234CrossRefPubMedGoogle Scholar
  57. Lee CJ, Lee MH, Yoo SM, Choi KI, Song JH, Jang JH, Oh SR, Ryu HW, Lee HS, Surh YJ, Cho YY (2015b) Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway. BMC Cancer 15:576CrossRefPubMedPubMedCentralGoogle Scholar
  58. Lim HC, Xie L, Zhang W, Li R, Chen ZC, Wu GZ, Cui SS, Tan EK, Zeng L (2013) Ribosomal S6 Kinase 2 (RSK2) maintains genomic stability by activating the Atm/p53-dependent DNA damage pathway. PLoS ONE 8:e74334CrossRefPubMedPubMedCentralGoogle Scholar
  59. Liu F, Thompson MA, Wagner S, Greenberg ME, Green MR (1993) Activating transcription factor-1 can mediate Ca(2 +)- and cAMP-inducible transcriptional activation. J Biol Chem 268:6714–6720PubMedGoogle Scholar
  60. Liu K, Cho YY, Yao K, Nadas J, Kim DJ, Cho EJ, Lee MH, Pugliese A, Zhang J, Bode AM, Dong Z, Dong Z (2011) Eriodictyol inhibits RSK2-ATF1 signaling and suppresses EGF-induced neoplastic cell transformation. J Biol Chem 286:2057–2066CrossRefPubMedGoogle Scholar
  61. Mayr B, Montminy M (2001) Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2:599–609CrossRefPubMedGoogle Scholar
  62. McCandless SE, Schwartz S, Morrison S, Garlapati K, Robin NH (2000) Adult with an interstitial deletion of chromosome 10 [del(10)(q25. 1q25.3)]: overlap with Coffin-Lowry syndrome. Am J Med Genet 95:93–98CrossRefPubMedGoogle Scholar
  63. Mueller PR, Coleman TR, Kumagai A, Dunphy WG (1995) Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15. Science 270:86–90CrossRefPubMedGoogle Scholar
  64. Myers AP, Corson LB, Rossant J, Baker JC (2004) Characterization of mouse Rsk4 as an inhibitor of fibroblast growth factor-RAS-extracellular signal-regulated kinase signaling. Mol Cell Biol 24:4255–4266CrossRefPubMedPubMedCentralGoogle Scholar
  65. Nathaniel-James DA, Frith CD (2002) The role of the dorsolateral prefrontal cortex: evidence from the effects of contextual constraint in a sentence completion task. Neuroimage 16:1094–1102CrossRefPubMedGoogle Scholar
  66. Neal JW, Clipstone NA (2003) A constitutively active NFATc1 mutant induces a transformed phenotype in 3T3-L1 fibroblasts. J Biol Chem 278:17246–17254CrossRefPubMedGoogle Scholar
  67. Norbury C, Nurse P (1992) Animal cell cycles and their control. Annu Rev Biochem 61:441–470CrossRefPubMedGoogle Scholar
  68. Palmer A, Gavin AC, Nebreda AR (1998) A link between MAP kinase and p34(cdc2)/cyclin B during oocyte maturation: p90(rsk) phosphorylates and inactivates the p34(cdc2) inhibitory kinase Myt1. EMBO J 17:5037–5047CrossRefPubMedPubMedCentralGoogle Scholar
  69. Parra MA, Kerr D, Fahy D, Pouchnik DJ, Wyrick JJ (2006) Deciphering the roles of the histone H2B N-terminal domain in genome-wide transcription. Mol Cell Biol 26:3842–3852CrossRefPubMedPubMedCentralGoogle Scholar
  70. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22:153–183PubMedGoogle Scholar
  71. Peng C, Cho YY, Zhu F, Xu YM, Wen W, Ma WY, Bode AM, Dong Z (2010) RSK2 mediates NF-{kappa}B activity through the phosphorylation of IkappaBalpha in the TNF-R1 pathway. FASEB J 24:3490–3499CrossRefPubMedPubMedCentralGoogle Scholar
  72. Peng C, Cho YY, Zhu F, Zhang J, Wen W, Xu Y, Yao K, Ma WY, Bode AM, Dong Z (2011) Phosphorylation of caspase-8 (Thr-263) by ribosomal S6 kinase 2 (RSK2) mediates caspase-8 ubiquitination and stability. J Biol Chem 286:6946–6954CrossRefPubMedGoogle Scholar
  73. Penn BH, Berkes CA, Bergstrom DA, Tapscott SJ (2001) How to MEK muscle. Mol Cell 8:245–246CrossRefPubMedGoogle Scholar
  74. Perry RL, Parker MH, Rudnicki MA (2001) Activated MEK1 binds the nuclear MyoD transcriptional complex to repress transactivation. Mol Cell 8:291–301CrossRefPubMedGoogle Scholar
  75. Peter ME, Krammer PH (2003) The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 10:26–35CrossRefPubMedGoogle Scholar
  76. Poon RY, Chau MS, Yamashita K, Hunter T (1997) The role of Cdc2 feedback loop control in the DNA damage checkpoint in mammalian cells. Cancer Res 57:5168–5178PubMedGoogle Scholar
  77. Rehfuss RP, Walton KM, Loriaux MM, Goodman RH (1991) The cAMP-regulated enhancer-binding protein ATF-1 activates transcription in response to cAMP-dependent protein kinase A. J Biol Chem 266:18431–18434PubMedGoogle Scholar
  78. Roux PP, Richards SA, Blenis J (2003) Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity. Mol Cell Biol 23:4796–4804CrossRefPubMedPubMedCentralGoogle Scholar
  79. Sassone-Corsi P, Mizzen CA, Cheung P, Crosio C, Monaco L, Jacquot S, Hanauer A, Allis CD (1999) Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. Science 285:886–891CrossRefPubMedGoogle Scholar
  80. Schaeffer HJ, Weber MJ (1999) Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 19:2435–2444CrossRefPubMedPubMedCentralGoogle Scholar
  81. Sebolt-Leopold JS, Herrera R (2004) Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 4:937–947CrossRefPubMedGoogle Scholar
  82. She QB, Ma WY, Zhong S, Dong Z (2002) Activation of JNK1, RSK2, and MSK1 is involved in serine 112 phosphorylation of Bad by ultraviolet B radiation. J Biol Chem 277:24039–24048CrossRefPubMedGoogle Scholar
  83. Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW (1999) Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo. J Biol Chem 274:2893–2898CrossRefPubMedGoogle Scholar
  84. Soloaga A, Thomson S, Wiggin GR, Rampersaud N, Dyson MH, Hazzalin CA, Mahadevan LC, Arthur JS (2003) MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. EMBO J 22:2788–2797CrossRefPubMedPubMedCentralGoogle Scholar
  85. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45CrossRefPubMedGoogle Scholar
  86. Sutherland C, Campbell DG, Cohen P (1993) Identification of insulin-stimulated protein kinase-1 as the rabbit equivalent of rskmo-2. Identification of two threonines phosphorylated during activation by mitogen-activated protein kinase. Eur J Biochem 212:581–588CrossRefPubMedGoogle Scholar
  87. Thomson S, Clayton AL, Hazzalin CA, Rose S, Barratt MJ, Mahadevan LC (1999) The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase. EMBO J 18:4779–4793CrossRefPubMedPubMedCentralGoogle Scholar
  88. Treisman R (1996) Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol 8:205–215CrossRefPubMedGoogle Scholar
  89. Trivier E, De Cesare D, Jacquot S, Pannetier S, Zackai E, Young I, Mandel JL, Sassone-Corsi P, Hanauer A (1996) Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. Nature 384:567–570CrossRefPubMedGoogle Scholar
  90. Tu VC, Sun H, Bowden GT, Chen QM (2007) Involvement of oxidants and AP-1 in angiotensin II-activated NFAT3 transcription factor. Am J Physiol Cell Physiol 292:C1248–1255CrossRefPubMedGoogle Scholar
  91. Wang Y, Prywes R (2000) Activation of the c-fos enhancer by the erk MAP kinase pathway through two sequence elements: the c-fos AP-1 and p62TCF sites. Oncogene 19:1379–1385CrossRefPubMedGoogle Scholar
  92. Ward IM, Chen J (2001) Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 276:47759–47762CrossRefPubMedGoogle Scholar
  93. Wei W, Jin J, Schlisio S, Harper JW, Kaelin WG Jr (2005) The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell 8:25–33CrossRefPubMedGoogle Scholar
  94. Wells NJ, Watanabe N, Tokusumi T, Jiang W, Verdecia MA, Hunter T (1999) The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with Cdc2 complexes and is required for inhibition of G(2)/M progression. J Cell Sci 112(Pt 19):3361–3371PubMedGoogle Scholar
  95. Yang TT, Xiong Q, Enslen H, Davis RJ, Chow CW (2002) Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases. Mol Cell Biol 22:3892–3904CrossRefPubMedPubMedCentralGoogle Scholar
  96. Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka HC, Schinke T, Li L, Brancorsini S, Sassone-Corsi P, Townes TM, Hanauer A, Karsenty G (2004) ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry syndrome. Cell 117:387–398CrossRefPubMedGoogle Scholar
  97. Yang TT, Xiong Q, Graef IA, Crabtree GR, Chow CW (2005) Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex. Mol Cell Biol 25:907–920CrossRefPubMedPubMedCentralGoogle Scholar
  98. Zaichuk TA, Shroff EH, Emmanuel R, Filleur S, Nelius T, Volpert OV (2004) Nuclear factor of activated T cells balances angiogenesis activation and inhibition. J Exp Med 199:1513–1522CrossRefPubMedPubMedCentralGoogle Scholar
  99. Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, Chen H, Jenner R, Herbolsheimer E, Jacobsen E, Kadam S, Ecker JR, Emerson B, Hogenesch JB, Unterman T, Young RA, Montminy M (2005) Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci USA 102:4459–4464CrossRefPubMedPubMedCentralGoogle Scholar
  100. Zhu F, Zykova TA, Peng C, Zhang J, Cho YY, Zheng D, Yao K, Ma WY, Lau AT, Bode AM, Dong Z (2011) Phosphorylation of H2AX at Ser139 and a new phosphorylation site Ser16 by RSK2 decreases H2AX ubiquitination and inhibits cell transformation. Cancer Res 71:393–403CrossRefPubMedGoogle Scholar

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© The Pharmaceutical Society of Korea 2016

Authors and Affiliations

  1. 1.College of PharmacyThe Catholic University of KoreaBucheon-siRepublic of Korea

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