Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate

@article{Santos2007GrowthFM,
  title={Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate},
  author={Silvia D. M. Santos and Peter J. Verveer and Philippe I. H. Bastiaens},
  journal={Nature Cell Biology},
  year={2007},
  volume={9},
  pages={324-330}
}
The mitogen-activated protein kinase (MAPK) network is a conserved signalling module that regulates cell fate by transducing a myriad of growth-factor signals. The ability of this network to coordinate and process a variety of inputs from different growth-factor receptors into specific biological responses is, however, still not understood. We investigated how the MAPK network brings about signal specificity in PC-12 cells, a model for neuronal differentiation. Reverse engineering by modular… Expand
Crosstalk and Signaling Switches in Mitogen-Activated Protein Kinase Cascades
TLDR
A dynamic model of feedback and crosstalk for the three major MAPK cascades is developed and it is shown that JNK can switch from a transient to sustained activity due to multiple positive feedback loops and abrogates the apoptotic switch explaining the failure of certain drugs to induce apoptosis. Expand
A two-dimensional ERK-AKT signaling code for an NGF-triggered cell-fate decision.
TLDR
A two-dimensional phospho-ERK (pERK)-phospho-AKT (pAKT) response map with a curved boundary that separates differentiating from proliferating cells is identified, and cells gain unique integration and control capabilities to balance cell number expansion with differentiation. Expand
Protein Arginine Methyltransferase 5 Regulates ERK1/2 Signal Transduction Amplitude and Cell Fate Through CRAF
TLDR
It is shown that protein arginine methylation limits the ERK1/2 signal elicited by particular growth factors in different cell types from various species, and this additional level of regulation within the RAS pathway may lead to the identification of new targets for therapeutic intervention. Expand
MAP Kinase activation by receptor tyrosine kinases: in control of cell migration.
TLDR
This work presents methods to identify key components of underlying cascades and their effects on the migratory phenotype, focusing on profiling activation of signaling modules, as well as transcriptional regulation, emphasizing the high-throughput potential of such approaches. Expand
KSR1 Modulates the Sensitivity of Mitogen-Activated Protein Kinase Pathway Activation in T Cells without Altering Fundamental System Outputs
TLDR
It is shown that T cells responded digitally to stimulation with superantigen-loaded antigen-presenting cells, whereas they responded in a graded manner to the chemokine SDF-1, demonstrating that the system output of theMAPK module is highly plastic and determined by components upstream of the MAPK module. Expand
The ERK mitogen-activated protein kinase signaling network: the final frontier in RAS signal transduction.
TLDR
Despite considerable advances in understanding the ERK-MAPK network, the ability of cancer cells to adapt to the inhibition of key nodes reveals a level of complexity that remains to be fully understood. Expand
Boolean Modeling Reveals the Necessity of Transcriptional Regulation for Bistability in PC12 Cell Differentiation
TLDR
The integrated model confirmed the parallel use of MAPK/ERK, PI3K/AKT, and JNK/JUN for PC12 cell differentiation and found that positive transcriptional feedback induces bistability in the cell fate switch. Expand
Extracellular‐regulated kinase—mitogen‐activated protein kinase cascade: Unsolved issues
  • J. Bodart
  • Biology, Medicine
  • Journal of cellular biochemistry
  • 2010
TLDR
Development of biophotonics strategies for monitoring the Erk network at the spatiotemporal level in living cells, as well as computational and hypothesis‐driven approaches, are called to unravel the principles by which signaling networks create biochemical and biological specificities. Expand
Systematic Quantification of Negative Feedback Mechanisms in the Extracellular Signal-regulated Kinase (ERK) Signaling Network*
TLDR
This work takes a systematic approach to parse the magnitudes of multiple regulatory mechanisms that attenuate ERK activation through canonical (Ras- dependent) and non-canonical (PI3K-dependent) pathways and demonstrates that kinetic models of signaling networks, trained on a sufficient diversity of quantitative data, can be reasonably comprehensive, accurate, and predictive in the dynamical sense. Expand
Receptor tyrosine kinases modulate distinct transcriptional programs by differential usage of intracellular pathways
TLDR
RNA-seq is performed to delineate the transcriptional response to platelet-derived growth factor and fibroblast growth factor signaling in mouse embryonic palatal mesenchyme cells, identifying distinct responses to PDGF and FGF and providing insight into the mechanisms encoding RTK specificity. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 27 REFERENCES
MAP Kinase Phosphatase As a Locus of Flexibility in a Mitogen-Activated Protein Kinase Signaling Network
TLDR
It is found that the growth factor–stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states, and MAPK phosphatase may be critical for this flexible response. Expand
Identification of the Mechanisms Regulating the Differential Activation of the MAPK Cascade by Epidermal Growth Factor and Nerve Growth Factor in PC12 Cells*
TLDR
Together, these data provide a signaling link between growth factor receptors and MAPK activation and a mechanistic explanation of the differential MAPK kinetics exhibited by these growth factors. Expand
Cross‐cascade activation of ERKs and ternary complex factors by Rho family proteins
TLDR
It is shown that Rho family small G proteins such as Rac1 and Cdc42hs, which activate the JNK/SAPK pathway, cooperate with Raf‐1 to activate the ERK pathway which causes activation of ternary complex factors, which regulate c‐fos gene expression through the serum response element. Expand
Mitogen-Activated Protein Kinase Feedback Phosphorylation Regulates MEK1 Complex Formation and Activation during Cellular Adhesion
TLDR
It is proposed that activation of ERK during adhesion creates a feedback system in which ERK phosphorylates MEK1 on T292, and this in turn blocks additional S298 phosphorylation in response to integrin signaling. Expand
Identification of novel in vivo Raf-1 phosphorylation sites mediating positive feedback Raf-1 regulation by extracellular signal-regulated kinase.
TLDR
This study describes the identification of new in vivo Raf-1 phosphorylation sites targeted by ERK and provides a novel mechanism for a positive feedback Raf-2 regulation, and its phosphopeptide composition is similar to that of the general Raf- 1 population. Expand
Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation
TLDR
Experiments with PC12 cells suggest that the duration of ERK activation is critical for cell signaling decisions, and the extracellular signal-regulated kinase (ERK-regulated) MAPK pathway may be sufficient for these cellular responses. Expand
Downregulation of the Ras activation pathway by MAP kinase phosphorylation of Sos.
TLDR
It is reported here that treatment of human peripheral blood T lymphoblasts with phorbol esters causes a similar shift in mobility of Sos, and a novel negative feedback mechanism therefore exists whereby activation of MAP kinases through Ras results in the uncoupling of the Sos/Grb2 complex from tyrosine kinase substrates without blocking the interaction of So with Grb2. Expand
Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase
TLDR
It is demonstrated that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggested therefore that the enzyme functions in vivo to integrate signals from two distinct transduction pathways. Expand
Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors
TLDR
The model provides insight into signal–response relationships between the binding of EGF to its receptor at the cell surface and the activation of downstream proteins in the signaling cascade, showing that EGF-induced responses are remarkably stable over a 100-fold range of ligand concentration. Expand
Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP
TLDR
RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK module and competitively disrupts the interaction between these kinases. Expand
...
1
2
3
...