Why Are Fibronectin and Integrin-5-Beta-1 In the Model?
Interestingly, the displayed EGF-to-Erk pathway also includes inputs from Fibronectin (FN) binding to its receptor integrin-5-beta-1. Here FN binding to this integrin receptor causes activation of p21-activated kinase 1 (Pak1) [12167697] which is required for activation of Raf1. Whether there are other protein kinases that phosphorylate Raf1 at the same site is unknown, and therefore only Pak1 activation is included in the present model. Biologically, attachment to a suitable substrate is necessary for most if not all adherent normal cells to survive and proliferate, particularly through Erk activation [8106557] [10777598]. See what happens when FN is removed from the model by the following operation. • Analyze, Edit Goals • Erk2-act-cm = Goal • Rafb-cyto = Avoid • FN-out = Avoid • Analyze, Find A Pathway The result, ‘Goal node is not reachable’, is consistent with the requirement for FN engagement (substrate adherence) for the activation of Erk2 in response to EGF stimulation.
