Scaffolds are ‘active’ regulators of signaling modules

@article{Alexa2010ScaffoldsA,
  title={Scaffolds are ‘active’ regulators of signaling modules},
  author={Anita Alexa and J{\'a}nos Varga and Attila Rem{\'e}nyi},
  journal={The FEBS Journal},
  year={2010},
  volume={277}
}
Signaling cascades, in addition to proteins with obvious signaling‐relevant activities (e.g. protein kinases or receptors), also employ dedicated ‘inactive’ proteins whose functions appear to be the organization of the former components into higher order complexes through protein–protein interactions. The core function of signaling adaptors, anchors and scaffolds is the recruitment of proteins into one macromolecular complex. Several recent studies have demonstrated that the recruiter and the… 
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References

SHOWING 1-10 OF 47 REFERENCES
Organizing signal transduction through A‐kinase anchoring proteins (AKAPs)
TLDR
A fundamental role for protein–protein interactions in the organization of signal transduction pathways is evident and selected A‐kinase anchoring protein signaling complexes are highlighted in this minireview.
Finding scaffold proteins in interactomes.
Membrane Recruitment of Scaffold Proteins Drives Specific Signaling
TLDR
The mechanisms presented here, which explain how the membrane recruitment of a protein can produce a drastic change in the activity of cells, are generic and may be commonly used in many biological processes.
Rewiring MAP Kinase Pathways Using Alternative Scaffold Assembly Mechanisms
TLDR
It is found that the yeast mitogen-activated protein (MAP) kinase scaffold Ste5 is tolerant to major stereochemical perturbations; heterologous protein interactions could functionally replace native kinase recruitment interactions, indicating that simple tethering is largely sufficient for scaffold-mediated signaling.
Scaffolding proteins organize multimolecular protein complexes for sensory signal transduction
  • A. Huber
  • Biology
    The European journal of neuroscience
  • 2001
TLDR
This review focuses on the INAD‐assembled signalling complex of Drosophila photoreceptors, which organizes key components of the phototransduction cascade into a multiprotein signal transduction unit.
KSR and CNK: two scaffolds regulating RAS-mediated RAF activation
TLDR
The possibility that KSR, a RAF-like protein, does not solely act as a scaffold, but directly induces RAF catalytic function by a kinase-independent mechanism apparently shared by RAF- like proteins is discussed.
Regulation of Signal Duration and the Statistical Dynamics of Kinase Activation by Scaffold Proteins
TLDR
Monte Carlo simulations of a model kinase cascade are used to investigate how the temporal characteristics of signaling cascades can be influenced by the presence of scaffold proteins, and provide insights into one mechanism that describes how the duration of a signal can potentially be regulated in a scaffold mediated protein Kinase cascade.
KSR is a scaffold required for activation of the ERK/MAPK module.
TLDR
It is suggested that KSR functions as a scaffold that assembles the RAF/MEK functional pair, and that these interactions lead to the formation of a RAF/ MEK complex, thereby positioning RAF in close proximity to its substrate MEK.
...
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