Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

RSK (p90 Ribosomal S6 Kinase)

Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_382


Historical Background

The p90 ribosomal S6 kinase (RSK) family comprises four mammalian Ser/Thr kinases (RSK1-4) (Romeo et al. 2012). The first RSK family member was identified as a kinase activity in maturating Xenopus laevis oocytes that phosphorylated the 40S ribosomal subunit protein S6 (rpS6) (Erikson and Maller 1985, 1986). Although the p70 ribosomal S6 kinases 1 and 2 (S6K1 and S6K2) were later shown to be the predominant S6 kinases operating in somatic cells (Blenis et al. 1991; Chung et al. 1992), RSK1 and RSK2 were found to phosphorylate rpS6 in response to ERK1/ERK2 pathway activation (Cohen et al. 2005; Roux et al. 2007). Interestingly, whereas S6K1/S6K2 phosphorylate all sites on rpS6 (Ser235, Ser236, Ser240, and Ser244), RSK1 and RSK2 were shown to specifically phosphorylate Ser235 and Ser236 (Roux et al. 2007). It should be noted, however, that the molecular mechanism(s) underlying the diverse effects of rpS6 phosphorylation on cellular and organismal physiology are still poorly understood (Meyuhas 2015).

Structure of the RSK Isoforms

The RSK isoforms are 73–80% identical to each other and are mostly divergent in their amino- and carboxyl-termini sequences. The structure of RSK is complex and comprises two functionally distinct kinase domains, a linker region, and N- and C-terminal tails. While the N-terminal-kinase domain (NTKD) shares homology with kinases of the AGC family (PKA, PKG, PKC), the C-terminal kinase domain (CTKD) is homologous to the calcium/calmodulin-dependent protein kinases (CaMKs). It is thought that during evolution, the genes for two different protein kinases have fused, generating a single polypeptide capable of receiving an upstream activating signal from the Ras/MAPK pathway to its CTKD and transmitting, with high efficiency and fidelity, an activating input to its NTKD. Thus, the CTKD appears to be only involved in autophosphorylation of RSK, resulting in its activation, and the NTKD is responsible for downstream substrate phosphorylation (Bjorbaek et al. 1995). The C-terminal tail contains an ERK1/ERK2 docking motif, known as the D domain, and interaction of RSK with ERK1/ERK2 was shown to depend on a short motif consisting of Leu-Arg-Gln-Arg-Arg (Roux et al. 2003; Smith et al. 1999). Finally, the C-terminal tail of all RSK isoforms contains a type 1 PDZ domain-binding motif, consisting of Thr-Xaa-Leu, where Xaa is any amino acid. This motif was shown to be functional with at least some PDZ domain-containing proteins (Thomas et al. 2005), but more work will be needed to fully determine its role and biological significance.

Activation Mechanisms

The RSK isoforms contain six phosphorylation sites that are responsive to mitogenic stimulation. Mutational analysis revealed that four of these sites (Ser221, Ser352, Ser369, and Thr562 in mouse RSK1) are essential for RSK activation (Dalby et al. 1998). Of these, Ser221 (located in the NTKD activation loop), Ser352 (turn motif), and Ser369 (hydrophobic motif) are located within sequences highly conserved in other AGC kinases (Newton 2003). The current model of RSK activation suggests that ERK and RSK form an inactive complex in quiescent cells that is facilitated by the D domain on RSK (Hsiao et al. 1994; Zhao et al. 1996). After mitogenic stimulation, ERK1/2 phosphorylate Thr562 in the activation loop of the CTKD (Sutherland et al. 1993) and possibly Thr348 and Ser352 in the linker region between the two kinase domains (Dalby et al. 1998). Activation of the CTKD leads to autophosphorylation at Ser369 (Vik and Ryder 1997), which creates a docking site for phosphoinositide-dependent protein kinase 1 (PDK1) (Frodin et al. 2000). In turn, PDK1 phosphorylates Ser221 in the activation loop of the NTKD (Jensen et al. 1999; Richards et al. 1999) and, along with phosphorylated Ser352 and Ser369, promote an intramolecular allosteric mechanism that allows the NTKD to phosphorylate downstream substrates (Frodin et al. 2002). RSK also autophosphorylates at a C-terminal residue that releases ERK1/ERK2 binding, presumably to allow these kinases to find their respective substrates throughout the cell (Roux et al. 2003).

The process of RSK activation is closely linked to ERK1/ERK2 activity, and MEK1/MEK2 inhibitors (U0126, PD98059, PD184352) have been widely used to study RSK function. Four different classes of RSK inhibitors targeting the NTKD (SL-0101, BI-D1870, LJH685) or the CTKD (FMK) have been identified (Aronchik et al. 2014; Cohen et al. 2005; Sapkota et al. 2007; Smith et al. 2005). While BI-D1870, SL-0101, and LJH685 are ATP-competitive inhibitors, FMK (fluoromethylketone) is an irreversible inhibitor that covalently modifies the CTKD of RSK1, RSK2, and RSK4. Like most pharmacological inhibitors of protein kinases, it should be noted that the RSK inhibitors were reported to inhibit additional protein kinases (Aronchik et al. 2014; Bain et al. 2007). Alternate mechanisms of activation for RSK have been described (Kang et al. 2008; Zaru et al. 2007), but these appear to be cell type and context specific. One of these involves tyrosine phosphorylation by Src, which was shown to stabilize the interaction between ERK and RSK and thereby increase the rate at which RSK becomes activated (Kang et al. 2008). Another mechanism involves regulation of the hydrophobic motif of RSK by the related enzymes, MAPK-activated protein kinases 2 and 3 (MK2/3), which can facilitate RSK activation upon stimulation of the stress-responsive p38 MAPK pathway (Zaru et al. 2007).

Biological Functions

RSK appears to be a multifunctional ERK1/ERK2 effector because it participates in various cellular processes (Cargnello and Roux 2011; Romeo et al. 2012). A recent proteomics study determined that RSK phosphorylates a large number of substrates in cells involved in a wide range of biological functions (Galan et al. 2014). Although a number of RSK functions can be deduced from the nature of its substrates, data from many groups point towards roles for the RSKs in nuclear signaling, cell cycle progression and cell proliferation, cell growth and protein synthesis, and cell migration and cell survival. RSK was found to regulate several transcription factors, including SRF, c-Fos, and Nur77. On the basis of its substrates, RSK seems to have important functions in cellular growth control and proliferation. RSK may stimulate cell cycle progression through the regulation of immediate early gene products, such as c-Fos, which promotes the expression of cyclin D1 during the G0/G1 transition to S phase. RSK may also promote proliferation by regulating cell growth-related protein synthesis. Indeed, RSK was found to regulate the tumor suppressor TSC2 and Raptor (Carriere et al. 2008; Roux et al. 2004) and thereby promote mTOR signaling in normal and cancer cells (Romeo et al. 2013). RSK has also been shown to regulate cell survival. RSK phosphorylates and inhibits the proapoptotic proteins Bad and DAPK, thereby promoting survival in response to mitogenic stimulation (Anjum et al. 2005; Shimamura et al. 2000). Many additional RSK substrates have been identified through the years, but at this point, very little is known regarding isoform specificity. Whereas more substrates have been identified for RSK2 than any other RSK isoforms, most studies have not determined isoform selectivity. Therefore, many known substrates of RSK2 may be shared by different RSK family members and more effort will be necessary to assess potential overlapping functions.

Physiological Functions

An important clue into the physiological roles of the RSK isoforms came from the finding that inactivating mutations in the Rps6ka3 gene (which encodes RSK2) were the cause of Coffin-Lowry syndrome (CLS)(Trivier et al. 1996). CLS is an X-linked mental retardation syndrome characterized in male patients by psychomotor retardation and facial, hand, and skeletal malformations (Pereira et al. 2010). Rps6ka3 mutations are extremely heterogeneous and lead to loss of phosphotransferase activity in the RSK2 kinase, most often because of premature termination of translation. It was shown that individuals with CLS consistently presented markedly reduced total brain volume, with cerebellum and hippocampal volumes being particularly impacted in CLS patients. The physiological role of RSK2 was also studied in the mouse through the generation of a deletion model. These mice were shown to have deficiencies in learning and cognitive functions, as well as having poor coordination compared to wild-type littermates (Dufresne et al. 2001; Poirier et al. 2007). The exact cause for these phenotypes remains unknown, but a recent study demonstrated that shRNA-mediated RSK2 depletion perturbs the differentiation of neural precursors into neurons and maintains them as proliferating radial precursor cells (Cargnello and Roux 2011; Romeo et al. 2012). Evidently, more experimentation using RSK2-deficient animals will be required to fully understand the developmental role of RSK2 in the nervous system.

Mice deficient in RSK2 expression also develop a progressive skeletal disease, called osteopenia, due to cell-autonomous defects in osteoblast activity (David et al. 2005). Both c-Fos and ATF4 transcription factors were shown to be critical RSK2 substrates involved in these effects in osteoblasts (Cargnello and Roux 2011; Romeo et al. 2012). In addition, RSK2 knockout mice are approximately 15% smaller than their wild-type littermates, with a specific loss of white adipose tissue that is accompanied by reduced serum levels of the adipocyte-derived peptide, leptin. RSK1/RSK2/RSK3 triple knockout mice are viable, but no other information regarding their phenotype has yet been reported (Cargnello and Roux 2011; Romeo et al. 2012). The Rps6ka6 gene (that codes for RSK4) is located on chromosome X and was suggested to be involved in nonspecific X-linked mental retardation, but definitive evidence remains to be provided. Interestingly, deletion of Drosophila RSK was found to result in defects in learning and conditioning (Putz et al. 2004). More recent work has shown that Drosophila RSK regulates synaptic function and axonal transport in motoneurons (Beck et al. 2015). RSK3 was shown to be important for pathological remodeling of the heart, as it appears to serve a unique role in cardiac myocyte in response to stress (Martinez et al. 2015). RSK4 is perhaps the least understood of RSK isoforms but was shown to inhibit cancer cell proliferation and perhaps promote cellular senescence (Arechavaleta-Velasco et al. 2016; Lopez-Vicente et al. 2011). Consistent with this, RSK4 appears to be downregulated in several types of cancer (Cai et al. 2014; Li et al. 2014; Rafiee et al. 2016).


Many studies have now clearly established RSK as an important effector of the Ras/MAPK pathway, and it is becoming increasingly clear RSK signaling is deregulated in several human diseases (Romeo and Roux 2011; Sulzmaier and Ramos 2013). Recent studies have expanded the repertoire of biological functions linked to the RSK family of protein kinases, ranging from the regulation of transcription, translation, and protein stability to the control of cell survival, cell motility, cell growth, and proliferation (Galan et al. 2014). It has become clear that other AGC family members such as Akt and S6K have similar functions and often share similar protein targets. These findings emphasize the importance of a tight and intricate regulation of cellular processes that are important for cell growth and cell survival. Combined, these studies have helped to identify additional targets for therapeutic intervention in diseases that are associated with inappropriate signaling downstream of Ras and Raf and reveal novel targets for biomarker development for disease detection.


  1. Anjum R, Roux PP, Ballif BA, Gygi SP, Blenis J. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Curr Biol. 2005;15:1762–7.PubMedCrossRefGoogle Scholar
  2. Arechavaleta-Velasco F, Zeferino-Toquero M, Estrada-Moscoso I, Imani-Razavi FS, Olivares A, Perez-Juarez CE, Diaz-Cueto L. Ribosomal S6 kinase 4 (RSK4) expression in ovarian tumors and its regulation by antineoplastic drugs in ovarian cancer cell lines. Med Oncol. 2016;33:11.PubMedCrossRefGoogle Scholar
  3. Aronchik I, Appleton BA, Basham SE, Crawford K, Del Rosario M, Doyle LV, Estacio WF, Lan J, Lindvall MK, Luu CA, et al. Novel potent and selective inhibitors of p90 ribosomal S6 kinase reveal the heterogeneity of RSK function in MAPK-driven cancers. Mol Cancer Res. 2014;12:803–12.PubMedCrossRefGoogle Scholar
  4. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, Cohen P. The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007;408:297–315.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Beck K, Ehmann N, Andlauer TF, Ljaschenko D, Strecker K, Fischer M, Kittel RJ, Raabe T. Loss of the Coffin-Lowry syndrome-associated gene RSK2 alters ERK activity, synaptic function and axonal transport in Drosophila motoneurons. Dis Model Mech. 2015;8:1389–400.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bjorbaek C, Zhao Y, Moller DE. Divergent functional roles for p90rsk kinase domains. J Biol Chem. 1995;270:18848–52.PubMedCrossRefGoogle Scholar
  7. Blenis J, Chung J, Erikson E, Alcorta DA, Erikson RL. 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. 1991;2:279–85.PubMedGoogle Scholar
  8. Cai J, Ma H, Huang F, Zhu D, Zhao L, Yang Y, Bi J, Zhang T. Low expression of RSK4 predicts poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 2014;7:4959–70.PubMedPubMedCentralGoogle Scholar
  9. Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011;75:50–83.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Carriere A, Cargnello M, Julien LA, Gao H, Bonneil E, Thibault P, Roux PP. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr Biol. 2008;18:1269–77.PubMedCrossRefGoogle Scholar
  11. Chung J, Kuo CJ, Crabtree GR, Blenis J. Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell. 1992;69:1227–36.PubMedCrossRefGoogle Scholar
  12. Cohen MS, Zhang C, Shokat KM, Taunton J. Structural bioinformatics-based design of selective, irreversible kinase inhibitors. Science. 2005;308:1318–21.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Dalby KN, Morrice N, Caudwell FB, 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. 1998;273:1496–505.PubMedCrossRefGoogle Scholar
  14. David JP, Mehic D, Bakiri L, Schilling AF, Mandic V, Priemel M, Idarraga MH, Reschke MO, Hoffmann O, Amling M, et al. Essential role of RSK2 in c-Fos-dependent osteosarcoma development. J Clin Invest. 2005;115:664–72.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Dufresne SD, Bjorbaek C, El-Haschimi K, Zhao Y, Aschenbach WG, Moller DE, Goodyear LJ. Altered extracellular signal-regulated kinase signaling and glycogen metabolism in skeletal muscle from p90 ribosomal S6 kinase 2 knockout mice. Mol Cell Biol. 2001;21:81–7.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Erikson E, Maller JL. A protein kinase from Xenopus eggs specific for ribosomal protein S6. Proc Natl Acad Sci U S A. 1985;82:742–6.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Erikson E, Maller JL. Purification and characterization of a protein kinase from Xenopus eggs highly specific for ribosomal protein S6. J Biol Chem. 1986;261:350–5.PubMedGoogle Scholar
  18. Frodin M, Jensen CJ, Merienne K, Gammeltoft S. A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1. EMBO J. 2000;19:2924–34.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Frodin M, Antal TL, Dummler BA, Jensen CJ, Deak M, Gammeltoft S, Biondi RM. A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation. EMBO J. 2002;21:5396–407.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Galan JA, Geraghty KM, Lavoie G, Kanshin E, Tcherkezian J, Calabrese V, Jeschke GR, Turk BE, Ballif BA, Blenis J, et al. Phosphoproteomic analysis identifies the tumor suppressor PDCD4 as a RSK substrate negatively regulated by 14-3-3. Proc Natl Acad Sci U S A. 2014;111:E2918–27.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Hsiao K-M, Chou S-Y, Shih S-J, Ferrell Jr JE. Evidence that inactive p42 mitogen-activated protein kinase and inactive Rsk exist as a heterodimer in vivo. Proc Natl Acad Sci U S A. 1994;91:5480–4.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Jensen CJ, Buch MB, Krag TO, Hemmings BA, Gammeltoft S, Frodin M. 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1. J Biol Chem. 1999;274:27168–76.PubMedCrossRefGoogle Scholar
  23. Kang S, Dong S, Guo A, Ruan H, Lonial S, Khoury HJ, Gu TL, Chen J. Epidermal growth factor stimulates RSK2 activation through activation of the MEK/ERK pathway and src-dependent tyrosine phosphorylation of RSK2 at Tyr-529. J Biol Chem. 2008;283:4652–7.PubMedCrossRefGoogle Scholar
  24. Li Q, Jiang Y, Wei W, Ji Y, Gao H, Liu J. Frequent epigenetic inactivation of RSK4 by promoter methylation in cancerous and non-cancerous tissues of breast cancer. Med Oncol. 2014;31:793.PubMedCrossRefGoogle Scholar
  25. Lopez-Vicente L, Pons B, Coch L, Teixido C, Hernandez-Losa J, Armengol G, Ramon YCS. RSK4 inhibition results in bypass of stress-induced and oncogene-induced senescence. Carcinogenesis. 2011;32:470–6.PubMedCrossRefGoogle Scholar
  26. Martinez EC, Passariello CL, Li J, Matheson CJ, Dodge-Kafka K, Reigan P, Kapiloff MS. RSK3: a regulator of pathological cardiac remodeling. IUBMB Life. 2015;67:331–7.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Meyuhas O. Ribosomal protein S6 phosphorylation: four decades of research. Int Rev Cell Mol Biol. 2015;320:41–73.PubMedCrossRefGoogle Scholar
  28. Newton AC. Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem J. 2003;370:361–71.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Pereira PM, Schneider A, Pannetier S, Heron D, Hanauer A. Coffin-Lowry syndrome. Eur J Hum Genet. 2010;18:627–33.PubMedCrossRefGoogle Scholar
  30. Poirier R, Jacquot S, Vaillend C, Soutthiphong AA, Libbey M, Davis S, Laroche S, Hanauer A, Welzl H, Lipp HP, 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. 2007;37:31–50.PubMedCrossRefGoogle Scholar
  31. 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. 2004;24:9745–51.PubMedCrossRefGoogle Scholar
  32. Rafiee M, Keramati MR, Ayatollahi H, Sadeghian MH, Barzegar M, Asgharzadeh A, Alinejad M. Down-regulation of ribosomal S6 kinase RPS6KA6 in acute myeloid leukemia patients. Cell J. 2016;18:159–64.PubMedPubMedCentralGoogle Scholar
  33. Richards SA, 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. 1999;9:810–20.PubMedCrossRefGoogle Scholar
  34. Romeo Y, Roux PP. Paving the way for targeting RSK in cancer. Expert Opin Ther Targets. 2011;15:5–9.PubMedCrossRefGoogle Scholar
  35. Romeo Y, Zhang X, Roux PP. Regulation and function of the RSK family of protein kinases. Biochem J. 2012;441:553–69.PubMedCrossRefGoogle Scholar
  36. Romeo Y, Moreau J, Zindy P-J, Saba-El-Leil M, Lavoie G, Dandachi F, Baptissart M, Borden KLB, Meloche S, Roux PP. RSK regulates activated BRAF signalling to mTORC1 and promotes melanoma growth. Oncogene. 2013;32:2917–26.PubMedCrossRefGoogle Scholar
  37. Roux PP, Richards SA, Blenis J. Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity. Mol Cell Biol. 2003;23:4796–804.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Roux PP, Ballif BA, Anjum R, Gygi SP, 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 U S A. 2004;101:13489–94.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Roux PP, Shahbazian D, Vu H, Holz MK, Cohen MS, Taunton J, Sonenberg N, Blenis J. RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation. J Biol Chem. 2007;282:14056–64.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Sapkota GP, Cummings L, Newell FS, Armstrong C, Bain J, Frodin M, Grauert M, Hoffmann M, Schnapp G, Steegmaier M, et al. BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J. 2007;401:29–38.PubMedCrossRefGoogle Scholar
  41. Shimamura A, Ballif BA, Richards SA, Blenis J. Rsk1 mediates a MEK-MAP kinase cell survival signal. Curr Biol. 2000;10:127–35.PubMedCrossRefGoogle Scholar
  42. Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW. 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. 1999;274:2893–8.PubMedCrossRefGoogle Scholar
  43. Smith JA, Poteet-Smith CE, Xu Y, Errington TM, Hecht SM, Lannigan DA. Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation. Cancer Res. 2005;65:1027–34.PubMedCrossRefGoogle Scholar
  44. Sulzmaier FJ, Ramos JW. RSK isoforms in cancer cell invasion and metastasis. Cancer Res. 2013;73:6099–105.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Sutherland C, Campbell DG, 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. 1993;212:581–8.PubMedCrossRefGoogle Scholar
  46. Thomas GM, Rumbaugh GR, Harrar DB, Huganir RL. Ribosomal S6 kinase 2 interacts with and phosphorylates PDZ domain-containing proteins and regulates AMPA receptor transmission. Proc Natl Acad Sci U S A. 2005;102(42):15006–11.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Trivier E, De Cesare D, Jacquot S, Pannetier S, Zackai E, Young I, Mandel JL, Sassone-Corsi P, Hanauer A. Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. Nature. 1996;384:567–70.PubMedCrossRefGoogle Scholar
  48. Vik TA, Ryder JW. Identification of serine 380 as the major site of autophosphorylation of Xenopus pp90rsk. Biochem Biophys Res Commun. 1997;235:398–402.PubMedCrossRefGoogle Scholar
  49. Zaru R, Ronkina N, Gaestel M, Arthur JS, 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. Nat Immunol. 2007;8:1227–35.PubMedCrossRefGoogle Scholar
  50. Zhao Y, Bjorbaek C, Moller DE. Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases. J Biol Chem. 1996;271:29773–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute for Research in Immunology and Cancer (IRIC), Department of Pathology and Cell Biology, Faculty of MedicineUniversité de MontréalMontrealCanada