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. 2008 Dec 22;29(5):1249–1265. doi: 10.1128/MCB.00853-08

FIG. 10.

FIG. 10.

Model of HRG/ErbB-2-induced Stat3 activation. HRG binding induces ErbB-2/ErbB-3 heterodimerization and the concomitant phosphorylation of ErbB-2 at the Tyr 1222 autophosphorylation site (1), which couples ErbB-2 to the MAPK cascade (2). On the other hand, HRG stimulates a first level of c-Src activation through a PR-independent mechanism (3). Jaks are also activated independently of PR (4). HRG-activated p42/p44 MAPKs induce the rapid phosphorylation of PR on Ser 294 (5). PR phosphorylated on Ser 294 then promotes a second round of c-Src activation (6). c-Src, dually activated firstly by ErbB-2 acting as an upstream effector and then by HRG-activated PR, acts in turn as an upstream modulator of ErbB-2 and induces its phosphorylation on Tyr 877 (7), with the latter being the molecular event that couples HRG/ErbB-2 to Stat3 activation (8).