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MPM cells were responsive to HGF (40 ng/mL) stimulation of c-Met signaling up to 5 hours in a time-dependent fashion (Fig. 2B). Significant induction of tyrosine phosphorylation in c-Met of the autophosphorylation site (pY1230/1234/1235) as well as the regulatory juxtamembrane c-Cbl binding site (pY1003) was evident starting at 15 minutes of HGF stimulation and the phospho-signal declined between 2 and 5 hours. Moreover, phosphorylation of ERK1/2 (pT185/pY187) and AKT (S473) was significantly induced in a differential manner with different cell lines after HGF stimulation (Fig. 2B).
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