The RSK family of kinases: emerging roles in cellular signalling (original) (raw)

• Roberts, P. J. & Der, C. J. Targeting the Raf–MEK–ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26, 3291–3310 (2007).
  Article CAS PubMed Google Scholar
• Roux, P. P. & Blenis, J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev. 68, 320–344 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Carriere, A., Ray, H., Blenis, J. & Roux, P. P. The RSK factors of activating the Ras/MAPK signaling cascade. Front. Biosci. 13, 4258–4275 (2008).
  Article CAS PubMed Google Scholar
• Jones, S. W., Erikson, E., Blenis, J., Maller, J. L. & Erikson, R. L. A Xenopus ribosomal protein S6 kinase has two apparent kinase domains that are each similar to distinct protein kinases. Proc. Natl Acad. Sci. USA 85, 3377–3381 (1988). Reported the compound nature of the kinase RSK for the first time and showed that RSK contains two apparent kinase domains, each similar to distinct protein kinases. It also reported that RSK has homology to other members of the AGC family of protein kinases.
  Article CAS PubMed PubMed Central Google Scholar
• Fisher, T. L. & Blenis, J. Evidence for two catalytically active kinase domains in pp90rsk. Mol. Cell. Biol. 16, 1212–1219 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, R. H., Sarnecki, C. & Blenis, J. Nuclear localization and regulation of _erk_- and _rsk_-encoded protein kinases. Mol. Cell. Biol. 12, 915–927 (1992). Demonstrated that ERK and RSK accumulate in the nucleus following growth-factor-dependent activation. It provided evidence for how signalling originating from the cell surface is transmitted into the nucleus to regulate agonist-dependent changes in nuclear function, such as induction of immediate-early gene expression.
  CAS PubMed PubMed Central Google Scholar
• Deak, M., Clifton, A. D., Lucocq, L. M. & Alessi, D. R. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 17, 4426–4441 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Pierrat, B., Correia, J. S., Mary, J. L., Tomas-Zuber, M. & Lesslauer, W. RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under dominant control of p38α mitogen-activated protein kinase (p38αMAPK). J. Biol. Chem. 273, 29661–29671 (1998).
  Article CAS PubMed Google Scholar
• Blenis, J. & Erikson, R. L. Phosphorylation of the ribosomal protein S6 is elevated in cells transformed by a variety of tumor viruses. J. Virol. 50, 966–969 (1984).
  Article CAS PubMed PubMed Central Google Scholar
• Nielsen, P. J., Thomas, G. & Maller, J. L. Increased phosphorylation of ribosomal protein S6 during meiotic maturation of Xenopus oocytes. Proc. NatlAcad. Sci. USA 79, 2937–2941 (1982).
  Article CAS Google Scholar
• Erikson, E. & Maller, J. L. A protein kinase from Xenopus eggs specific for ribosomal protein S6. Proc. Natl Acad. Sci. USA 82, 742–746 (1985).
  Article CAS PubMed PubMed Central Google Scholar
• Sturgill, T. W., Ray, L. B., Erikson, E. & Maller, J. L. Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II. Nature 334, 715–718 (1988). The first demonstration of a protein kinase (RSK) that is phosphorylated and activated downstream of the ERK/MAPK cascade.
  Article CAS PubMed Google Scholar
• Fingar, D. C. & Blenis, J. Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 23, 3151–3171 (2004).
  Article CAS Google Scholar
• Blenis, J., Chung, J., Erikson, E., Alcorta, D. A. & Erikson, R. L. Distinct mechanisms for the activation of the RSK kinases/MAP2 kinase/pp90rsk and pp70–S6 kinase signaling systems are indicated by inhibition of protein synthesis. Cell Growth Differ. 2, 279–285 (1991).
  CAS PubMed Google Scholar
• Chung, J., Kuo, C. J., Crabtree, G. R. & Blenis, J. Rapamycin–FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell 69, 1227–1236 (1992).
  Article CAS PubMed Google Scholar
• Schwab, M. S. et al. p70S6K controls selective mRNA translation during oocyte maturation and early embryogenesis in Xenopus laevis. Mol. Cell. Biol. 19, 2485–2494 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Roux, P. P. et al. RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation. J. Biol. Chem. 282, 14056–14064 (2007).
  Article CAS PubMed Google Scholar
• Richards, S. A., Dreisbach, V. C., Murphy, L. O. & Blenis, J. Characterization of regulatory events associated with membrane targeting of p90 ribosomal S6 kinase 1. Mol. Cell. Biol. 21, 7470–7480 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Murphy, L. O., Smith, S., Chen, R. H., Fingar, D. C. & Blenis, J. Molecular interpretation of ERK signal duration by immediate early gene products. Nature Cell Biol. 4, 556–564 (2002).
  Article CAS PubMed Google Scholar
• Dummler, B. A. et al. Functional characterization of human RSK4, a new 90-kDa ribosomal S6 kinase, reveals constitutive activation in most cell types. J. Biol. Chem. 280, 13304–13314 (2005).
  Article PubMed CAS Google Scholar
• Zhao, Y., Bjorbaek, C., Weremowicz, S., Morton, C. C. & Moller, D. E. RSK3 encodes a novel pp90rsk isoform with a unique N-terminal sequence: growth factor-stimulated kinase function and nuclear translocation. Mol. Cell. Biol. 15, 4353–4363 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Zeniou, M., Ding, T., Trivier, E. & Hanauer, A. Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin–Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning. Hum. Mol. Gen. 11, 2929–2940 (2002).
  Article CAS PubMed Google Scholar
• Bjorbaek, C., Zhao, Y. & Moller, D. E. Divergent functional roles for p90rsk kinase domains. J. Biol. Chem. 270, 18848–18852 (1995).
  Article CAS PubMed Google Scholar
• Roux, P. P., Richards, S. A. & Blenis, J. Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity. Mol. Cell. Biol. 23, 4796–4804 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Gavin, A. C., Ni Ainle, A., Chierici, E., Jones, M. & Nebreda, A. R. A p90rsk mutant constitutively interacting with MAP kinase uncouples MAP kinase from p34cdc2/cyclin B activation in Xenopus oocytes. Mol. Biol. Cell 10, 2971–2986 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Dalby, K. N., Morrice, N., Caudwell, F. B., Avruch, J. & Cohen, P. Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK. J. Biol. Chem. 273, 1496–1505 (1998).
  Article CAS PubMed Google Scholar
• Jensen, C. J. et al. 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1. J. Biol. Chem. 274, 27168–27176 (1999). Provided evidence for the phosphorylation of RSK2 by PDK1, thus extending the findings which implicated PDK1 in the activation of AKT/PKB, PKC and S6K, and suggesting that PDK1 controls several crucial growth factor-activated signal-transduction pathways.
  Article CAS PubMed Google Scholar
• McManus, E. J. et al. The in vivo role of PtdIns(3,4,5)P3 binding to PDK1 PH domain defined by knockin mutation. EMBO J. 23, 2071–2082 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Mora, A., Komander, D., van Aalten, D. M. & Alessi, D. R. PDK1, the master regulator of AGC kinase signal transduction. Semin. Cell Dev. Biol. 15, 161–170 (2004).
  Article CAS PubMed Google Scholar
• McCoy, C. E., Campbell, D. G., Deak, M., Bloomberg, G. B. & Arthur, J. S. MSK1 activity is controlled by multiple phosphorylation sites. Biochem. J. 387, 507–517 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Williams, M. R. et al. The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells. Curr. Biol. 10, 439–448 (2000).
  Article CAS PubMed Google Scholar
• Frodin, M. et al. A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation. EMBO J. 21, 5396–5407 (2002).
  Article PubMed PubMed Central Google Scholar
• Newton, A. C. Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem. J. 370, 361–371 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Frodin, M., Jensen, C. J., Merienne, K. & Gammeltoft, S. A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1. EMBO J. 19, 2924–2934 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Richards, S. A., Fu, J., Romanelli, A., Shimamura, A. & Blenis, J. Ribosomal S6 kinase 1 (RSK1) activation requires signals dependent on and independent of the MAP kinase ERK. Curr. Biol. 9, 810–820 (1999).
  Article CAS PubMed Google Scholar
• Sutherland, C., Campbell, D. G. & Cohen, P. 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, 581–588 (1993).
  Article CAS PubMed Google Scholar
• Smith, J. A., Poteet-Smith, C. E., Malarkey, K. & Sturgill, T. W. 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, 2893–2898 (1999).
  Article CAS PubMed Google Scholar
• Zaru, R., Ronkina, N., Gaestel, M., Arthur, J. S. & Watts, C. The MAPK-activated kinase Rsk controls an acute Toll-like receptor signaling response in dendritic cells and is activated through two distinct pathways. Nature Immunol. 8, 1227–1235 (2007). Demonstrated that Toll-like receptor-dependent activation of RSK is activated not only by ERK but also by p38 through the intermediates MK2 and MK3.
  Article CAS Google Scholar
• Ranganathan, A., Pearson, G. W., Chrestensen, C. A., Sturgill, T. W. & Cobb, M. H. The MAP kinase ERK5 binds to and phosphorylates p90 RSK. Arch. Biochem. Biophys. 449, 8–16 (2006).
  Article CAS PubMed Google Scholar
• Kang, S. et al. FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway. Cancer Cell 12, 201–214 (2007). The first evidence that RSK2 is phosphorylated on Tyr by FGFR3, which enhances its binding and activation by ERK.
  Article CAS PubMed PubMed Central Google Scholar
• Wood, K. W., Sarnecki, C., Roberts, T. M. & Blenis, J. ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK. Cell 68, 1041–1050 (1992). The first to show that the Ras GTPase mediates signal transmission from several growth factors and tumour promoters to the ERK/MAPK module leading to RSK activation.
  Article CAS PubMed Google Scholar
• Doehn, U., Gammeltoft, S., Shen, S. H. & Jensen, C. J. p90 ribosomal S6 kinase 2 is associated with and dephosphorylated by protein phosphatase 2Cδ. Biochem. J. 382, 425–431 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Kim, M. et al. Inhibition of ERK–MAP kinase signaling by RSK during Drosophila development. EMBO J. 25, 3056–3067 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Chaturvedi, D., Poppleton, H. M., Stringfield, T., Barbier, A. & Patel, T. B. Subcellular localization and biological actions of activated RSK1 are determined by its interactions with subunits of cyclic AMP-dependent protein kinase. Mol. Cell. Biol. 26, 4586–4600 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Leighton, I. A., Dalby, K. N., Caudwell, F. B., Cohen, P. T. & Cohen, P. Comparison of the specificities of p70 S6 kinase and MAPKAP kinase-1 identifies a relatively specific substrate for p70 S6 kinase: the N-terminal kinase domain of MAPKAP kinase-1 is essential for peptide phosphorylation. FEBS Lett. 375, 289–293 (1995).
  Article CAS PubMed Google Scholar
• McManus, M. T. & Sharp, P. A. Gene silencing in mammals by small interfering RNAs. Nature Rev. Genet. 3, 737–747 (2002).
  Article CAS PubMed Google Scholar
• Trivier, E. et al. Mutations in the kinase Rsk-2 associated with Coffin–Lowry syndrome. Nature 384, 567–570 (1996). Provides the first direct evidence that abnormalities in the MAPK–RSK signalling pathway cause Coffin–Lowry syndrome.
  Article CAS PubMed Google Scholar
• Frodin, M. & Gammeltoft, S. Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Mol. Cell. Endocrinol. 151, 65–77 (1999).
  Article CAS PubMed Google Scholar
• De Cesare, D., Jacquot, S., Hanauer, A. & Sassone-Corsi, P. 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, 12202–12207 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Bruning, J. C. et al. Ribosomal subunit kinase-2 is required for growth factor-stimulated transcription of the c-Fos gene. Proc. Natl Acad. Sci. USA 97, 2462–2467 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Arthur, J. S. & Cohen, P. MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells. FEBS Lett. 482, 44–48 (2000).
  Article CAS PubMed Google Scholar
• Chen, R. H., Abate, C. & Blenis, J. Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase. Proc. Natl Acad. Sci. USA 90, 10952–10956 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Wingate, A. D., Campbell, D. G., Peggie, M. & Arthur, J. S. Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation. Biochem. J. 393, 715–724 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Nakajima, T. et al. The signal-dependent coactivator CBP is a nuclear target for pp90RSK. Cell 86, 465–474 (1996).
  Article CAS PubMed Google Scholar
• Joel, P. B. et al. pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167. Mol. Cell. Biol. 18, 1978–1984 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Wu, J. & Janknecht, R. Regulation of the ETS transcription factor ER81 by the 90-kDa ribosomal S6 kinase 1 and protein kinase A. J. Biol. Chem. 277, 42669–42679 (2002).
  Article CAS PubMed Google Scholar
• Zhao, J., Yuan, X., Frodin, M. & Grummt, I. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth. Mol. Cell 11, 405–413 (2003).
  Article CAS PubMed Google Scholar
• Wu, M. et al. c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Genes Dev. 14, 301–312 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Sutherland, C., Leighton, I. A. & Cohen, P. Inactivation of glycogen synthase kinase-3 β by phosphorylation: new kinase connections in insulin and growth-factor signalling. Biochem. J. 296, 15–19 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Diehl, J. A., Cheng, M., Roussel, M. F. & Sherr, C. J. Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 12, 3499–3511 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Sears, R. et al. Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev. 14, 2501–2514 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Nikolakaki, E., Coffer, P. J., Hemelsoet, R., Woodgett, J. R. & Defize, L. H. Glycogen synthase kinase 3 phosphorylates Jun family members in vitro and negatively regulates their transactivating potential in intact cells. Oncogene 8, 833–840 (1993).
  CAS PubMed Google Scholar
• Zhu, J., Blenis, J. & Yuan, J. Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1. Proc. Natl Acad. Sci. USA 105, 6584–6589 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Holland, E. C., Sonenberg, N., Pandolfi, P. P. & Thomas, G. Signaling control of mRNA translation in cancer pathogenesis. Oncogene 23, 3138–3144 (2004).
  Article CAS PubMed Google Scholar
• Angenstein, F., Greenough, W. T. & Weiler, I. J. Metabotropic glutamate receptor-initiated translocation of protein kinase p90rsk to polyribosomes: a possible factor regulating synaptic protein synthesis. Proc. Natl Acad. Sci. USA 95, 15078–15083 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Roux, P. P., Ballif, B. A., Anjum, R., Gygi, S. P. & Blenis, J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc. Natl Acad. Sci. USA 101, 13489–13494 (2004). Provides the first evidence for crosstalk between the Ras–MAPK–RSK pathway and the mTOR pathway via RSK-mediated phosphorylation and inactivation of TSC2. This paper also provides an example of signals from the PI3K pathway (via AKT/PKB) and the Ras pathway (via RSK) converging on a single target (TSC2), to more potently suppress its function via phosphorylation of distinct sites.
  Article CAS PubMed PubMed Central Google Scholar
• Manning, B. D. & Cantley, L. C. AKT/PKB signaling: navigating downstream. Cell 129, 1261–1274 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Carrière, A. et al. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr. Biol. 21 Aug 2008 (doi: 10.1016/j.cub.2008.07.078).
  Article PubMed CAS Google Scholar
• Shahbazian, D. et al. The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity. EMBO J. 25, 2781–2791 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Rozen, F. et al. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. Mol. Cell. Biol. 10, 1134–1144 (1990).
  CAS PubMed PubMed Central Google Scholar
• Holz, M. K., Ballif, B. A., Gygi, S. P. & Blenis, J. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell 123, 569–580 (2005).
  Article CAS PubMed Google Scholar
• Etchison, D., Milburn, S. C., Edery, I., Sonenberg, N. & Hershey, J. W. Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000-dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex. J. Biol. Chem. 257, 14806–14810 (1982).
  Article CAS PubMed Google Scholar
• Raught, B. et al. Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases. EMBO J. 23, 1761–1769 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Pende, M. et al. S6K1−/−/S6K2−/− mice exhibit perinatal lethality and rapamycin-sensitive 5′-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway. Mol. Cell. Biol. 24, 3112–3124 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Cohen, P. & Frame, S. The renaissance of GSK3. Nature Rev. Mol. Cell Biol. 2, 769–776 (2001).
  Article CAS Google Scholar
• Wang, X. et al. Regulation of elongation factor 2 kinase by p90RSK1 and p70 S6 kinase. EMBO J. 20, 4370–4379 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Ballif, B. A. & Blenis, J. Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)–MAPK cell survival signals. Cell Growth Differ. 12, 397–408 (2001).
  CAS PubMed Google Scholar
• Shimamura, A., Ballif, B. A., Richards, S. A. & Blenis, J. Rsk1 mediates a MEK–MAP kinase cell survival signal. Curr. Biol. 10, 127–135 (2000).
  Article CAS PubMed Google Scholar
• Bonni, A. et al. Cell survival promoted by the Ras–MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 286, 1358–1362 (1999).
  Article CAS PubMed Google Scholar
• Tan, Y., Ruan, H., Demeter, M. R. & Comb, M. J. p90RSK blocks Bad-mediated cell death via a protein kinase C-dependent pathway. J. Biol. Chem. 274, 34859–34867 (1999). References 78–80 show how the PI3K pathway (via AKT/PKB) and the Ras pathway (via RSK) converge on a single target, the BH3-only protein BAD, to more potently suppress its pro-apoptotic function via phosphorylation of distinct sites.
  Article CAS PubMed Google Scholar
• Anjum, R., Roux., P. P., Ballif, B. A., Gygi, S. P. & Blenis, J. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Curr. Biol. 15, 1762–1767 (2005).
  Article CAS PubMed Google Scholar
• Buck, M., Poli, V., Hunter, T. & Chojkier, M. C/EBPβ phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival. Mol. Cell 8, 807–816 (2001).
  Article CAS PubMed Google Scholar
• Ginty, D. D., Bonni, A. & Greenberg, M. E. Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell 77, 713–725 (1994).
  Article PubMed Google Scholar
• Xing, J., Ginty, D. D. & Greenberg, M. E. Coupling of the RAS–MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 273, 959–963 (1996).
  Article CAS PubMed Google Scholar
• Ghoda, L., Lin, X. & Greene, W. C. The 90-kDa ribosomal S6 kinase (pp90rsk) phosphorylates the N-terminal regulatory domain of IκBα and stimulates its degradation in vitro. J. Biol. Chem. 272, 21281–21288 (1997).
  Article CAS PubMed Google Scholar
• Schouten, G. J. et al. IκB α is a target for the mitogen-activated 90 kDa ribosomal S6 kinase. EMBO J. 16, 3133–3144 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Fujita, N., Sato, S. & Tsuruo, T. Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization. J. Biol. Chem. 278, 49254–49260 (2003).
  Article CAS PubMed Google Scholar
• Nebreda, A. R. & Ferby, I. Regulation of the meiotic cell cycle in oocytes. Curr. Opin. Cell Biol 12, 666–675 (2000).
  Article CAS PubMed Google Scholar
• Palmer, A., Gavin, A. C. & Nebreda, A. R. A link between MAP kinase and p34cdc2/cyclin B during oocyte maturation: p90rsk phosphorylates and inactivates the p34cdc2 inhibitory kinase Myt1. EMBO J. 17, 5037–5047 (1998). The identification of the first downstream kinase target of RSK, MYT1, extending the ERK cascade and providing a direct link to the cell-cycle machinery.
  Article CAS PubMed PubMed Central Google Scholar
• Bhatt, R. R. & Ferrell, J. E. Jr. The protein kinase p90 rsk as an essential mediator of cytostatic factor activity. Science 286, 1362–1365 (1999).
  Article CAS PubMed Google Scholar
• Gross, S. D., Schwab, M. S., Lewellyn, A. L. & Maller, J. L. Induction of metaphase arrest in cleaving Xenopus embryos by the protein kinase p90Rsk. Science 286, 1365–1367 (1999).
  Article CAS PubMed Google Scholar
• Schwab, M. S. et al. Bub1 is activated by the protein kinase p90Rsk during Xenopus oocyte maturation. Curr. Biol. 11, 141–150 (2001).
  Article CAS PubMed Google Scholar
• Inoue, D., Ohe, M., Kanemori, Y., Nobui, T. & Sagata, N. A direct link of the Mos–MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs. Nature 446, 1100–1104 (2007).
  Article CAS PubMed Google Scholar
• Nishiyama, T., Ohsumi, K. & Kishimoto, T. Phosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs. Nature 446, 1096–1099 (2007).
  Article CAS PubMed Google Scholar
• Woo, M. S., Ohta, Y., Rabinovitz, I., Stossel, T. P. & Blenis, J. Ribosomal S6 kinase (RSK) regulates phosphorylation of filamin A on an important regulatory site. Mol. Cell. Biol. 24, 3025–3035 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Wong, E. V., Schaefer, A. W., Landreth, G. & Lemmon, V. Involvement of p90rsk in neurite outgrowth mediated by the cell adhesion molecule L1. J. Biol. Chem. 271, 18217–18223 (1996).
  Article CAS PubMed Google Scholar
• Yoon, S. O. et al. Ran-binding protein 3 phosphorylation links the Ras and PI3-kinase pathways to nucleocytoplasmic transport. Mol. Cell 29, 362–375 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Song, T. et al. p90 RSK-1 associates with and inhibits neuronal nitric oxide synthase. Biochem. J. 401, 391–398 (2007).
  Article CAS PubMed Google Scholar
• Takahashi, E. et al. p90RSK is a serum-stimulated Na+/H+ exchanger isoform-1 kinase. Regulatory phosphorylation of serine 703 of Na+/H+ exchanger isoform-1. J. Biol. Chem. 274, 20206–20214 (1999).
  Article CAS PubMed Google Scholar
• Geraghty, K. M. et al. Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR. Biochem. J. 407, 231–241 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Silverman, E., Frodin, M., Gammeltoft, S. & Maller, J. L. Activation of p90 Rsk1 is sufficient for differentiation of PC12 cells. Mol. Cell. Biol. 24, 10573–10583 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Bignone, P. A. et al. RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer. Oncogene 26, 683–700 (2007).
  Article CAS PubMed Google Scholar
• Berns, K. et al. A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428, 431–437 (2004).
  Article CAS PubMed Google Scholar
• Thakur, A. et al. Aberrant expression of X-linked genes RbAp46, Rsk4, and Cldn2 in breast cancer. Mol. Cancer Res. 5, 171–181 (2007).
  Article CAS PubMed Google Scholar
• Myers, A. P., Corson, L. B., Rossant, J. & Baker, J. C. Characterization of mouse Rsk4 as an inhibitor of fibroblast growth factor-RAS-extracellular signal-regulated kinase signaling. Mol. Cell. Biol. 24, 4255–4266 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Smith, J. A. et al. Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation. Cancer research 65, 1027–1034 (2005).
  Article CAS PubMed Google Scholar
• Clark, D. E. et al. The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferation. Cancer Res. 65, 3108–3116 (2005).
  Article CAS PubMed Google Scholar
• Cohen, M. S., Zhang, C., Shokat, K. M. & Taunton, J. Structural bioinformatics-based design of selective, irreversible kinase inhibitors. Science 308, 1318–1321 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Sapkota, G. P. et al. BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem. J. 401, 29–38 (2007).
  Article CAS PubMed Google Scholar
• Bain, J. et al. The selectivity of protein kinase inhibitors: a further update. Biochem. J. 408, 297–315 (2007). Comparative characterization of newly identified RSK inhibitors first described in references 106–108.
  Article CAS PubMed PubMed Central Google Scholar
• Dumont, J., Umbhauer, M., Rassinier, P., Hanauer, A. & Verlhac, M. H. p90Rsk is not involved in cytostatic factor arrest in mouse oocytes. J. Cell Biol. 169, 227–231 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Dufresne, S. D. et al. Altered extracellular signal-regulated kinase signaling and glycogen metabolism in skeletal muscle from p90 ribosomal S6 kinase 2 knockout mice. Mol. Cell. Biol. 21, 81–87 (2001). Using Rsk2 -knockout mice, this study shows that RSK2 probably has a major role in feedback inhibition of the ERK pathway in skeletal muscle.
  Article CAS PubMed PubMed Central Google Scholar
• Poirier, R. et al. Deletion of the Coffin–Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior. Behav. Genet. 37, 31–50 (2007).
  Article CAS PubMed Google Scholar
• El-Haschimi, K. et al. Insulin resistance and lipodystrophy in mice lacking ribosomal S6 kinase 2. Diabetes 52, 1340–1346 (2003).
  Article CAS PubMed Google Scholar
• Putz, G., Bertolucci, F., Raabe, T., Zars, T. & Heisenberg, M. The S6KII (rsk) gene of Drosophila melanogaster differentially affects an operant and a classical learning task. J. Neurosci. 24, 9745–9751 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Tomas-Zuber, M., Mary, J. L., Lamour, F., Bur, D. & Lesslauer, W. C-terminal elements control location, activation threshold, and p38 docking of ribosomal S6 kinase B (RSKB). J. Biol. Chem. 276, 5892–5899 (2001).
  Article CAS PubMed Google Scholar
• Wiggin, G. R. et al. MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts. Mol. Cell. Biol. 22, 2871–2881 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Soloaga, A. et al. MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. EMBO J. 22, 2788–2797 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Arthur, J. S. et al. Mitogen- and stress-activated protein kinase 1 mediates cAMP response element-binding protein phosphorylation and activation by neurotrophins. J. Neurosci. 24, 4324–4332 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Schuck, S., Soloaga, A., Schratt, G., Arthur, J. S. & Nordheim, A. The kinase MSK1 is required for induction of c-fos by lysophosphatidic acid in mouse embryonic stem cells. BMC Mol. Biol. 4, 6 (2003).
  Article PubMed PubMed Central Google Scholar
• Yntema, H. G. et al. A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation. Genomics 62, 332–343 (1999).
  Article CAS PubMed Google Scholar
• Dimitri, C. A., Dowdle, W., MacKeigan, J. P., Blenis, J. & Murphy, L. O. Spatially separate docking sites on ERK2 regulate distinct signaling events in vivo. Curr. Biol. 15, 1319–1324 (2005).
  Article CAS PubMed Google Scholar