Hepatocytes are responsive to mitogenic effects of several ligands acting via EGFR. Studying primary cultures of rat hepatocytes, we found that, as compared to EGF, HB-EGF had a markedly higher affinity of the EGFR, while AR and TGFα had lower affinity. HB-EGF was also more potent compared to the other growth factors regarding phosphorylation of EGFR, Shc, ERK1/2 and Akt. All ligands induced phosphorylation of ErbB2, indicating receptor heterodimerization. TGFα, despite having much lower receptor affinity, was about equally potent and efficacious as HB-EGF as a stimulator of DNA synthesis. In contrast, EGF had relatively high affinity but markedly lower efficacy in stimulation of DNA synthesis. The results suggest that amplifying and/or inhibitory mechanisms may modulate the mitogenic responses downstream of the initial signalling steps, and that this may affect the effects of the EGFR ligands differentially.

肝细胞对通过EGFR作用的几种配体的促有丝分裂作用有反应。通过研究大鼠肝细胞的原代培养，我们发现，与EGF相比，HB-EGF与EGFR的亲和力明显更高，而AR和TGFα的亲和力更低。与其他生长因子相比，HB-EGF在EGFR，Shc，ERK1 / 2和Akt的磷酸化方面也更有效。所有配体均诱导ErbB2磷酸化，表明受体异源二聚化。尽管TGFα具有较低的受体亲和力，但它作为刺激DNA合成的HB-EGF具有同等效力和效​​力。相比之下，EGF具有相对较高的亲和力，但在刺激DNA合成方面功效明显较低。结果表明，放大和/或抑制机制可能会调节初始信号传导步骤下游的促有丝分裂反应，