Shc-dependent pathway is redundant but dominant in MAPK cascade activation by EGF receptors: a computational result

Yunchen Gong1, Xin Zhao2, McGill University;, McGill University

Cell signaling cascades usually do not occur in the manner of one stimulus - one pathway - one physiological consequence. Perturbation of one pathway by blocking or overexpressing a component in it 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 with the well-established modeling software, GEPASI, we find that the Shc-dependent pathway is both redundant and dominant during activation of MAPK 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 determining the dominance are the binding and phosphorylation of Shc, especially the latter one. The relative importance of two sub-pathways in the Shc-dependent pathway is also discussed. Results imply that organisms may use the longer pathway rather than the shorter alternative pathway for signal transduction.