Shc‐dependent pathway is redundant but dominant in MAPK cascade activation by EGF receptors: a modeling inference

In cell signaling cascades, one stimulus often leads to various physiological functions by multiple pathways. Perturbation of one pathway by blocking or overexpressing one of its components will result in changes in multiple pathways and multiple cell functions. Thus, it is important to reveal the relative contribution of each pathway to each function in order to assess the consequence of perturbations (e.g. drug delivery). By exploring an established mathematical model, the Shc-dependent pathway is found to be both redundant and dominant during activation of the mitogen-activated protein kinase cascade by epidermal growth factor receptor (EGFR). Its dominance results from the majority consumption of the common precursor ((EGF-EGFR*)2-GAP) by this pathway. The key steps for the dominance are the binding and phosphorylation of Shc. In conclusion, cells may prefer the long Shc-dependent pathway to the short Shc-independent pathway.