EGFR signaling patterns are regulated by its different ligands

Stine Louise Jeppe Knudsen; Anni Sieu Wai Mac; Lasse Henriksen; Bo van Deurs; Lene Melsæther Grøvdal

doi:10.3109/08977194.2014.952410

EGFR signaling patterns are regulated by its different ligands

Growth Factors. 2014 Oct;32(5):155-63. doi: 10.3109/08977194.2014.952410.

Authors

Stine Louise Jeppe Knudsen¹, Anni Sieu Wai Mac, Lasse Henriksen, Bo van Deurs, Lene Melsæther Grøvdal

Affiliation

¹ Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen , Denmark .

PMID: 25257250
DOI: 10.3109/08977194.2014.952410

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.

Keywords: BTC; EGF; EGF receptor; HB-EGF; TGFα; signaling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding, Competitive
Epidermal Growth Factor / metabolism
ErbB Receptors / metabolism*
HeLa Cells
Heparan Sulfate Proteoglycans / metabolism
Heparin-binding EGF-like Growth Factor / metabolism
Humans
Inhibitory Concentration 50
Ligands*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Phospholipase C gamma / metabolism
Phosphorylation
Protein Binding
Proto-Oncogene Proteins c-akt / metabolism
Receptor, ErbB-4 / metabolism
STAT3 Transcription Factor / metabolism
Signal Transduction*
Tumor Necrosis Factor-alpha / metabolism

Substances

Heparan Sulfate Proteoglycans
Heparin-binding EGF-like Growth Factor
Ligands
STAT3 Transcription Factor
STAT3 protein, human
Tumor Necrosis Factor-alpha
Epidermal Growth Factor
ERBB4 protein, human
ErbB Receptors
Receptor, ErbB-4
Proto-Oncogene Proteins c-akt
MAPK1 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Phospholipase C gamma