STAT3 is one of the potential downstream mediators for multiple growth factors acting on the pancreatic β-cells, including betacellulin, hepatocyte growth factor, growth hormone, and heparin-binding EGF-like growth factor.
In contrast to master regulators the so called mid-level regulators can not only be mediators of different incoming regulatory signals but also influence multiple downstream components or pathways.
Both upstream and downstream mediators and networks are interlinked, impairing cellular bioenergetic and metabolic function at multiple levels, and resulting in organ dysfunction [ 7, 23- 25].
The example of GM-CSF mediated induction of IL-1β, a known mediator of atherosclerosis, provides an illustration of how CX3CL1 and GM-CSF may have multiple downstream effects to augment atherosclerosis.
These data indicate that HDAC4 is a novel inflammatory pain mediator and may be a good therapeutic target, capable of orchestrating the regulation of multiple downstream effectors. Crow, M., Khovanov, N., Kelleher, J. H., Sharma, S., Grant, A. D., Bogdanov, Y., Wood, J. N., McMahon, S. B., Denk, F. HDAC4 is required for inflammation-associated thermal hypersensitivity.
In this study, we examined downstream mediators of NO/PARP activation to investigate possible mediators of ischemic sexual dimorphism.
Furthermore, we show that downstream mediators of IGF signaling (e.g. phospho-Akt and mTOR) are required for this effect.
We hypothesized that CD95 signaling, via tyrosine phosphorylation and recruitment of downstream mediators, might induce an EMT signal that can promote stemness and invasive migration in GBM cells.
After establishing this cellular model, we next wanted to test the recruitment of known downstream mediators of non-apoptotic CD95 signals.
PDF has been shown to trigger multiple downstream effects even within the same neuron.
