RSK and MSK in MAP kinase signalling

Hauge, Camilla; Frödin, Morten

doi:10.1242/jcs.02950

Cited by 186 publications

(157 citation statements)

References 14 publications

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“…Interestingly a number of studies have shown that the MAPK pathway plays an important role in mitotic activity of progenitor cells in the developing CNS as well as in the neurogenic niche of the adult SGZ (Alonso et al 2004;Choi et al 2008). Some of the effects of MAPK signaling on proliferation have been ascribed to the effector kinase RSK (Zhang and Liu 2002;Hauge and Frodin 2006), whereas the role of other kinase pathways has not been well established. Clearly, the work presented here provides an interesting context within which to examine the precise mechanism by which MSK1 affects progenitor proliferation as well as neurogenesis.…”

Section: Msk1 and Progenitor Proliferation And Neurogenesismentioning

confidence: 99%

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

et al. 2012

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Environmental enrichment (EE) has marked beneficial effects on cognitive capacity. Given the possibility that this form of neuronal plasticity could function via the actuation of the same cellular signaling pathways that underlie learning/memory formation, we examined whether the MAPK cascade effector, mitogen/stress-activated kinase 1 (MSK1), could play a role in this process. MSK1 functions as a key signaling intermediate that couples changes in neuronal activity into inducible gene expression, neuronal plasticity, and learning/memory. Here, we show that MSK1 is expressed in excitatory cell layers of the hippocampus, progenitor cells of the subgranular zone (SGZ), and adult-born immature neurons. MSK1 2/2 mice exhibit reduced spinogenesis and decreased dendritic branching complexity in hippocampal neurons, compared with WT mice. Further, in MSK1 2/2 mice, progenitor cell proliferation within the SGZ was significantly reduced and, correspondingly, the number of immature neurons within the dentate gyrus was significantly reduced. Consistent with prior work, MSK1 2/2 mice displayed deficits in both spatial and recognition memory tasks. Strikingly, cognitive enhancement resulting from a 40-d period of EE was markedly reduced in MSK1 2/2 animals. MSK1 2/2 mice exhibited reduced levels of EE-induced spinogenesis and SGZ progenitor proliferation. Taken together, these data reveal that MSK1 serves as a critical regulator of hippocampal physiology and function and that MSK1 serves as a key conduit by which enriching stimuli augment cellular plasticity and cognition.

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Section: Msk1 and Progenitor Proliferation And Neurogenesismentioning

confidence: 99%

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

et al. 2012

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“…RSK orthologs have been identified in mouse, rat, chicken Xenopus laevis, and Drosophila. 21 The various RSK proteins are all widely expressed in mammals and many cell types express several members. In human and mouse embryonic brain, as well as in adult mouse brain, the highest levels of RSK2 expression are observed in regions with high synaptic activity, including the neocortex, the hippocampus, and Purkinje cells, which are essential components in cognitive function and learning.…”

Section: Rsk2 Protein Functionmentioning

confidence: 99%

“…The N-terminal kinase domain phosphorylates downstream targets and is activated through a sequential phosphorylation cascade involving PDK1, the C-terminal kinase domain of RSK, and ERK1/2. 21 In addition, it has recently been shown that FGFR3, by interacting with, and phosphorylating two tyrosine residues within the C-terminal region of RSK2, influences RSK2 activation. 23 Altogether, the data provide evidence that RSKs have an important role in cell-cycle progression, differentiation, and cell survival.…”

Section: Rsk2 Protein Functionmentioning

confidence: 99%

“…23 Altogether, the data provide evidence that RSKs have an important role in cell-cycle progression, differentiation, and cell survival. 21 In the cytosol, RSK proteins have been shown to phosphorylate many substrates, including GSK3, L1CAM, the Ras GEF-Sos, IkB, the p34cdc2-inhibitory kinase Myt1, the translation factors eEF2, eIF4B, and the pro-apoptotic protein BAD (Figure 2). Moreover, upon activation a fraction of the cytosolic RSK molecule translocates to the nucleus in which it is thought to regulate gene expression through phosphorylation of transcription factors, such as CREB 1, ERa, Nurr 77, and SRF, as well as histones.…”

Section: Rsk2 Protein Functionmentioning

confidence: 99%

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Coffin–Lowry syndrome

et al. 2009

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Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation, which is characterized in male patients by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological signs in the hand are useful aids in the diagnosis. CLS is caused by mutations in the RPS6KA3 gene located at Xp22.2, which encodes RSK2, a growth-factor-regulated protein kinase. RPS6KA3 mutations are extremely heterogeneous and lead to loss of phosphotransferase activity in the RSK2 kinase, most often because of premature termination of translation.

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“…22,31 Ser 102 can be phosphorylated by Akt, PKCα, and RSK by binding to RxRxxS, RR/FRRK/RxS, and R/KxRxxS motifs. 22,32 Therefore, we incubated primary CD4 + T cells during anti-CD3/anti-CD28 stimulation and spontaneously proliferating Jurkat cells with the respective kinase inhibitors. Flow cytometric analysis of nuclear YB-1 protein in CD4 + T cells revealed that the Akt inhibitor II exerted only a minor effect, whereas treatment with Figure 1 YB-1 protein expression in primary and malignant human CD4 + T cells.…”

Section: Yb-1 Localization In the T-cell Nuclei Is Stimulation Dependmentioning

confidence: 99%

RSK-mediated nuclear accumulation of the cold-shock Y-box protein-1 controls proliferation of T cells and T-ALL blasts

et al. 2016

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Deregulated proliferation is key to tumor progression. Although unrestricted proliferation of solid tumor cells correlates with the cold-shock protein Y-box (YB)-binding protein-1 accumulation in the nuclei, little is known about its expression and function in hematopoietic malignancies, such as T-cell acute lymphoblastic leukemia (T-ALL). Here we show that YB-1 protein is highly enriched in the nuclei of activated T cells and malignant human T-ALL cell lines but not in resting T cells. YB-1 S 102 mutations that either mimic (S102D) or prevent phosphorylation (S102N) led to accumulation of YB-1 in the nucleus of T cells or strictly excluded it, respectively. Inactivation of ribosomal S6 kinase (RSK) was sufficient to abrogate T-cell and T-ALL cell proliferation, suggesting that RSK mediates cell-cycle progression, possibly dependent on YB-1-phosphorylation. Indeed, phosphomimetic YB-1 S102D enhanced proliferation implying that S 102 phosphorylation is a prerequisite for malignant T-cell proliferation. At initial diagnosis of T-ALL, YB-1 localization was significantly altered in the nuclei of tumor blasts derived from bone marrow or peripheral blood. Our data show deregulated YB-1 in the nucleus as a yet unreported characteristic of T-ALL blasts and may refine strategies to restrict progression of hematopoietic tumors.

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RSK and MSK in MAP kinase signalling

Cited by 186 publications

References 14 publications

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

Coffin–Lowry syndrome

RSK-mediated nuclear accumulation of the cold-shock Y-box protein-1 controls proliferation of T cells and T-ALL blasts

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