Thus, multiple signaling inputs can up-regulate uPAR transcription in tumors.
At the level of cellular control of membrane potential we wish to understand GIRK's AND/OR relationship with respect to multiple signaling inputs.
The context-dependence of TCFs is also apparent in other systems, for example in the embryonic midgut of Drosophila where dTCF integrates multiple signaling inputs with lineage-specific cues during endoderm induction (Riese et al., 1997).
Based upon our understanding that there are likely multiple positive signaling inputs (signaling pathway crosstalk) along the Src, Stat3, Myc pathway (eg. Stat3 can also be activated by Jak2 in addition to Src), it seems desirable to suppress the pathway at multiple levels to achieve a maximal effect under a variety of cellular conditions.
DOI: http://dx.doi.org/10.7554/eLife.06559.002 Cellular signaling pathways often exhibit a bowtie topology (Csete and Doyle, 2004): multiple distinct signal inputs converge on a single master regulator, typically a transcription factor (TF), which then controls the expression of partially overlapping sets of downstream target genes.
Likewise, redundancy is often observed between the inputs of multiple signalling pathways, presenting a significant obstacle in using individual signalling pathway inhibitors in the treatment of cancer and inflammatory conditions 94, 95.
A general coregulator such as Gro/TLE makes a perfect integrator of inputs from RTK signal transduction cascades with multiple signalling networks.
However, we hypothesized that regulation of gastrin by IL1B would depend on the cell's ability to integrate inputs from multiple signaling pathways to generate appropriate biological response.
Alternatively, the phosphorylation of ERK1/2 in TERT-siSFRP1 cells may require input from multiple signaling pathways.
The ultimate cellular response reflects the input of multiple signaling networks and does not result from a key "molecular target" or dedicated signaling pathway.
