Fig. 5
From: Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma
Integrin is important in hepatocyte growth factor (HGF)/Met signaling and AXT050 efficiently blocks the Met/α5β1 interaction (a). The model predicts that the response without α5β1 contribution meaning the condition that HGF (40 ng/ml) only signaled through Met and not Met-α5β1 (red) is considerably lower than when Met is allowed to interact with α5β1 (blue). The quantitation of the total number of phosphorylated proteins in a cell showed phosphorylated AKT (pAkt) levels to be more dependent on Met/α5β1 interaction than pERK and pMet levels (b). Most of the pMet signal (73%) was from pMeti signaling form endosomes compared to surface pMet (second row compared to first row). Increase in HGF concentration boosted steady-state pAkt and pERK response, but the transient phosphorylation peaks at earlier timepoints were higher in magnitude (c). AXT050 treatment efficiently blocked pAkt with pERK being less affected by the treatment (d)
