Activation of RSK by UV-light: phosphorylation dynamics and involvement of the MAPK pathway

Mérienne, Karine; Jacquot, Sylvie; Zeniou, Maria; Pannetier, Solange; Sassone–Corsi, Paolo; Hanauer, André

doi:10.1038/sj.onc.1203712

Cited by 43 publications

(35 citation statements)

References 57 publications

(67 reference statements)

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“…T147 mutants were obtained by sitedirected mutagenesis as described (37). GFP-PLD1, RSK2, RSK2 S227A, and T577A tagged with HA in pTL1 vectors have been described (13,19).…”

Section: Methodsmentioning

confidence: 99%

“…To establish whether RSK2 isoform plays a role in exocytosis, we first examined in PC12 cells the effect of two dominantnegative mutants of RSK2 (RSK2 S227A or RSK2 T577A ) unable to be phosphorylated (19), by using growth hormone (GH) secretion as a reporter assay for exocytosis. Expression of both RSK mutants strongly inhibited K ϩ -evoked GH secretion ( Fig.…”

Section: Rsk2 Ismentioning

confidence: 99%

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The Coffin–Lowry syndrome-associated protein RSK2 is implicated in calcium-regulated exocytosis through the regulation of PLD1

Zeniou-Meyer

Liu

Béglé

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Exocytosis of neurotransmitters and hormones occurs through the fusion of secretory vesicles with the plasma membrane. This highly regulated process involves key proteins, such as SNAREs, and specific lipids at the site of membrane fusion. Phospholipase D (PLD) has recently emerged as a promoter of membrane fusion in various exocytotic events potentially by providing fusogenic cone-shaped phosphatidic acid. We show here that PLD1 is regulated by ribosomal S6 kinase 2 (RSK2)-dependent phosphorylation. RSK2 is activated by a high K + -induced rise in cytosolic calcium. Expression of inactive RSK2 mutants or selective knockdown of endogenous RSK2 dramatically affects the different kinetic components of the exocytotic response in chromaffin cells. RSK2 physically interacts with and stimulates PLD activity through the phosphorylation of Thr-147 in the PLD1 amino-terminal phox homology domain. Expression of PLD1 phosphomimetic mutants fully restores secretion in cells depleted of RSK2, suggesting that RSK2 is a critical upstream signaling element in the activation of PLD1 to produce the lipids required for exocytosis. We propose that PLD-related defects in neuronal and endocrine activities could contribute to the effect observed after the loss-of-function mutations in Rsk2 that lead to Coffin–Lowry syndrome, an X-linked form of growth and mental retardation.

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“…T147 mutants were obtained by sitedirected mutagenesis as described (37). GFP-PLD1, RSK2, RSK2 S227A, and T577A tagged with HA in pTL1 vectors have been described (13,19).…”

Section: Methodsmentioning

confidence: 99%

Section: Rsk2 Ismentioning

confidence: 99%

The Coffin–Lowry syndrome-associated protein RSK2 is implicated in calcium-regulated exocytosis through the regulation of PLD1

Zeniou-Meyer

Liu

Béglé

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…There is accumulating evidence that support the existence of such a crosstalk, including: (1) voltage-gated K + channel activity involved in cell proliferation (Lu et al, 1993;Xu et al, 1996); (2) Kv channel activity regulated by growth factors (Xu et al, 1999;Roderick et al, 2003); and (3) Kv channel activity associated with Src tyrosine kinase (Holmes et al, 1996;Nitabach et al, 2001). More importantly, portions of the MAP kinase signaling pathways, including JNK/SAPK and p38 signaling pathways, mediate UV irradiation-induced corneal epithelial cell apoptosis (Adler et al, 1996;Price et al, 1996;Merienne et al, 2000;Bodero et al, 2003;Lu et al, 2003). Activation of ICE (caspase 1) can affect upstream events in the JNK pathway at the JNK level Lei et al, 1998).…”

Section: Uv-induced K + Channel and Jnk Activationmentioning

confidence: 99%

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

2006

Progress in Retinal and Eye Research

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One of the functional roles of the corneal epithelial layer is to protect the cornea, lens and other underlying ocular structures from damages caused by environmental insults. It is important for corneal epithelial cells to maintain this function by undergoing continuous renewal through a dynamic process of wound healing. Previous studies in corneal epithelial cells have provided substantial evidence showing that environmental insults, such as ultraviolet (UV) irradiation and other biohazards, can induce stress-related cellular responses resulting in apoptosis and thus interrupt the dynamic process of wound healing. We found that UV irradiation-induced apoptotic effects in corneal epithelial cells are started by the hyperactivation of K + channels in the cell membrane resulting in a fast loss of intracellular K + ions. Recent studies provide further evidence indicating that these complex responses in corneal epithelial cells are resulted from the activation of stressrelated signaling pathways mediated by K + channel activity. The effect of UV irradiation on corneal epithelial cell fate shares common signaling mechanisms involving the activation of intracellular responses that are often activated by the stimulation of various cytokines. One piece of evidence for making this distinction is that at early times UV irradiation activates a Kv3.4 channel in corneal epithelial cells to elicit activation of c-Jun N-terminal kinase cascades and p53 activation leading to cell cycle arrest and apoptosis. The hypothetic model is that UV-induced potassium channel hyperactivity as an early event initiates fast cell shrinkages due to the loss of intracellular potassium, resulting in the activation of scaffolding protein kinases and cytoskeleton reorganizations. This review article presents important control mechanisms that determine Kv channel activity-mediated cellular responses in corneal epithelial cells, involving activation of stress-induced signaling pathways, arrests of cell cycle progression and/or induction of apoptosis.

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“…Antibody to phospho-Thr 581 , raised against RSK2, is described in Ref. 44. Anti-HA Ab used for immunoprecipitation was from the 12CA5 mouse hybridoma cell line.…”

Section: Methodsmentioning

confidence: 99%

Functional Characterization of Human RSK4, a New 90-kDa Ribosomal S6 Kinase, Reveals Constitutive Activation in Most Cell Types

Dümmler

Hauge

Silber

et al. 2005

Journal of Biological Chemistry

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The 90-kDa ribosomal S6 kinases (RSK1-3) are important mediators of growth factor stimulation of cellular proliferation, survival, and differentiation and are activated via coordinated phosphorylation by ERK and 3-phosphoinositide-dependent protein kinase-1 (PDK1). Here we performed the functional characterization of a predicted new human RSK homologue, RSK4. We showed that RSK4 is a predominantly cytosolic protein with very low expression and several characteristics of the RSK family kinases, including the presence of two functional kinase domains and a C-terminal docking site for ERK. Surprisingly, however, in all cell types analyzed, endogenous RSK4 was maximally ( cdc2 -inhibitory kinase Myt1 (7) and the protein kinase Bub1 (8), respectively. In somatic cell types, RSK may stimulate cell division through phosphorylation of substrates like p27 Kip1 (9) and glycogen synthase kinase-3 (10 -12); protein synthesis and cell growth through substrates like elongation factor 2 kinase (13), glycogen synthase kinase-3 (10 -12), transcription initiation factor IA (14), and tuberous sclerosis complex-2 protein (15); cell survival through Bad (16); and transcription through substrates like c-Fos (17) and estrogen receptor (18). Experiments with PC12 cells suggest that RSK is a key mediator of ERK in neurotrophin-induced neuronal differentiation (19). Finally genetic evidence from human and mouse has identified an important role for RSK2 in osteoblast differentiation and function through phosphorylation of activating transcription factor-4 (20) and in stimulation of white adipose tissue mass via an unknown mechanism (21). RSK is related to the mitogen-and stress-activated protein kinases (MSK1 and MSK2), which also contain two kinase domains. MSK, however, is activated by the ERK family as well as by p38 family MAP kinases and thereby functions in signal transduction of growth factors as well as of cellular stress stimuli like UV/radioactive irradiation and proinflammatory cytokines (22,23).The substrates of RSK are phosphorylated by the N-terminal kinase (NTK) domain (24 -27) whose activity is regulated by

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Activation of RSK by UV-light: phosphorylation dynamics and involvement of the MAPK pathway

Cited by 43 publications

References 57 publications

The Coffin–Lowry syndrome-associated protein RSK2 is implicated in calcium-regulated exocytosis through the regulation of PLD1

The Coffin–Lowry syndrome-associated protein RSK2 is implicated in calcium-regulated exocytosis through the regulation of PLD1

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

Functional Characterization of Human RSK4, a New 90-kDa Ribosomal S6 Kinase, Reveals Constitutive Activation in Most Cell Types

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