The EGF subfamily of receptor protein tyrosine kinases mediates cellular proliferation, differentiation and transformation. Previously, we demonstrated that EGF is a potent and effective HASM cell mitogen; EGF also markedly enhanced PI 3-kinase activity. In this study, we demonstrate that the effects of EGF on HASM cell growth are mediated by activation of ErbB2 receptors. The addition of 10 ng/ml EGF to HASM cells induces a rapid increase in tyrosine phosphorylated cellular proteins and phosphorylates tyrosine residues on EGF and ErbB2 receptors. The ErbB2 tyrosine phosphorylation occurs within 30 sec and persists for 20 min. In response to EGF stimulation, PI 3-kinase activation is associated with ErbB2, but not with the EGF receptor. No effect on DNA synthesis and no change in phosphotyrosine levels are found in heregulin-treated (100 ng/ml) HASM cells. Heregulin, a specific agonist of ErbB3 and ErbB4, does not induce tyrosine phosphorylation of ErbB2 in HASM cells. ErbB2 activation, therefore, may play a critical role in regulating the mitogenic effects of EGF in non-transformed HASM cells.
|Original language||English (US)|
|State||Published - Dec 1 1997|
All Science Journal Classification (ASJC) codes
- Molecular Biology