Coupling of the RAS-MAPK Pathway to Gene Activation by RSK2, a Growth Factor-Regulated CREB Kinase

@article{Xing1996CouplingOT,
  title={Coupling of the RAS-MAPK Pathway to Gene Activation by RSK2, a Growth Factor-Regulated CREB Kinase},
  author={Jun Xing and David D. Ginty and Michael Eldon Greenberg},
  journal={Science},
  year={1996},
  volume={273},
  pages={959 - 963}
}
A signaling pathway has been elucidated whereby growth factors activate the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB), a critical regulator of immediate early gene transcription. Growth factor-stimulated CREB phosphorylation at serine-133 is mediated by the RAS-mitogen-activated protein kinase (MAPK) pathway. MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of… 
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1,273 Citations

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Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms.
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The molecular mechanisms by which Ser133-phosphorylated CREB activates transcription, intracellular signaling pathways that lead to phosphorylation ofCREB at Ser133, and features of each signaling pathway that impart specificity at the level of CREB activation are discussed.
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It is shown that embryonic fibroblasts from the S133A-knockin mice show that Ser133 phosphorylation downstream of PKA is required for CBP/p300 recruitment, and MSK-mediated CREB phosphorylated is critical for the induction of CREB-dependent genes downstream of MAPK signalling.
Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction
A Protein Kinase C-, Ras-, and RSK2-dependent Signal Transduction Pathway Activates the cAMP-responsive Element-binding Protein Transcription Factor following T Cell Receptor Engagement*
TLDR
Experiments are consistent with a model in which TCR engagement leads to the rapid phosphorylation and activation of CREB via a signaling pathway involving the activation of p56 lck, PKC, Ras, Raf-1, MEK, and RSK2.
Hypoxia Induces Phosphorylation of the Cyclic AMP Response Element-binding Protein by a Novel Signaling Mechanism*
TLDR
A physiological reduction in O2 levels induces a functional phosphorylation of CREB at Ser133 via a novel signaling pathway, more robust than that induced by any other stimulus tested, including forskolin, depolarization, and osmotic stress.
The Mitogen-Activated Protein Kinase Cascade Couples PKA and PKC to cAMP Response Element Binding Protein Phosphorylation in Area CA1 of Hippocampus
TLDR
An unexpected richness of diversity in the regulation of MAPK in the hippocampus is observed and the possibility of a broad role for the MAPK cascade in regulating gene expression in long-term forms of hippocampal synaptic plasticity is suggested.
Transcription Factor Phosphorylation by pp90 rsk2
TLDR
The in vitro phosphorylation of transcription factors by growth factor-activated protein kinases has resulted in the discovery of a number of activities whose identities and relationships to one another are unclear, and Fos kinase and NGFI-B kinase I and pp90 rsk2 represent the same protein kinase species.
Mitogen- and Stress-Activated Protein Kinase 1 Mediates cAMP Response Element-Binding Protein Phosphorylation and Activation by Neurotrophins
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It is shown here that neurotrophin-induced CREB phosphorylation in CNS neurons depends exclusively on the extracellular signal-regulated kinase 1/2-activated kinase mitogen- and stress-activated protein kinases 1 (MSK1).
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