EGFR signaling patterns are regulated by its different ligands

Abstract

EGF receptor (EGFR) and its signaling have been investigated for many years, but how its different ligands regulate signaling has not been thoroughly explored. When investigating EGFR activation and downstream signaling in HeLa cells using a panel of ligands, we found a ligand-dependent differential activation of EGFR and the signaling pathways Akt, PLCγ and STAT with HB-EGF and BTC being the most potent ligands. All the tested ligands induced full activation of Erk signaling at 1 nM, whereas only HB-EGF and partly BTC and EGF induced strong activation of Akt, STAT3 and PLCγ at this concentration. Interestingly, we also found that the high activation potencies of HB-EGF and BTC could only partially be explained by their binding affinities, and are therefore likely to be regulated by other mechanisms. We thus suggest that the signaling pathways initiated from the EGFR vary depending on the ligands bound in a cell specific manner.

• BTC
• EGF
• EGF receptor
• HB-EGF
• TGFα
• signaling

Acknowledgements

We thank Mette Ohlsen and Ulla Hjortenberg for excellent technical assistance and Michael Vibo Grandal, Vibeke Bertelsen, Espen Stang, Stefanie Thiele and Julie Lyng Forman for discussion and help with technical issues and interpretations of results.

Supplementary material available online.

Supplemental Figures S1–S3.