The Epidermal Growth Factor Receptor Couples Transforming Growth Factor-α, Heparin-binding Epidermal Growth Factor-like Factor, and Amphiregulin to Neu, ErbB-3, and ErbB-4

The epidermal growth factor (EGF) family hormones amphiregulin (AR), transforming growth factor-alpha (TGF-alpha), and heparin-binding EGF-like growth factor (HB-EGF) are thought to play significant roles in the genesis or progression of a number of human malignancies. However, the ability of these ligands to activate all four erbB family receptors has not been evaluated. Therefore, we have assessed the stimulation of erbB family receptor tyrosine phosphorylation by these hormones in a panel of mouse Ba/F3 cell lines expressing the four erbB family receptors, singly and in pairwise combinations. We also measured the stimulation of interleukin-3-independent survival or proliferation in this panel of Ba/F3 cell lines to compare the patterns of erbB family receptor coupling to physiologic responses induced by these peptides. EGF, TGF-alpha, AR, and HB-EGF all stimulated qualitatively similar patterns of erbB family receptor tyrosine phosphorylation and coupling to physiologic responses. Therefore, EGF, TGF-alpha, AR, and HB-EGF are functionally identical in this model system and behave differently from the EGF family hormones betacellulin and neuregulins.