This effect was associated with the inhibition of multiple kinase pathways including MAPK, PI3K/AKT, and NF-κB signaling pathways.
For example, the kinase networks shown in Figs.
Kinase substrate arrays can be used for parallel analysis of multiple kinase activities, which is called kinome profiling.
Interactions of multiple kinases in the signal transduction network lead to different outcomes in response to stimuli, which affects cell fate.
These results indicate a phosphorylation-dependent tuning of the period length by a regulatory network of multiple kinases and reveal an essential role of CaMKII in the cellular oscillation mechanism.
This data begins to enable "polypharmacological" targeting of multiple kinases [7 9], which may more effectively modify network behavior [10], or forestall drug resistance [11, 12], or provide broader applicability against heterogeneous cancers or larger patient groups.
Wound healing is a complex process that utilizes a network of signaling pathways activated by different stimuli and can converge upon multiple kinases to regulate gene expression, proliferation, and survival of the cell.
Therefore, more sophisticated models containing not only inhibitory molecules but also the complex involvement of multiple kinases are required for further clarification of the regulatory mechanisms underlying the increase in the phosphorylation rate on a network-wide scale.
Upon extracellular stimuli multiple kinases, such as protein kinase A, protein kinase C and casein kinase II, phosphorylate CREB at serine 133 (P-CREB) leading to activation of immediate early gene c-fos [3, 4].
For instance, phosphatase sharing between multiple kinases is ubiquitous within the MAPK pathway.
