Different Epidermal Growth Factor Receptor (EGFR) Agonists Produce Unique Signatures for the Recruitment of Downstream Signaling Proteins.

The Journal of Biological Chemistry
Tom RonanLinda J Pike

Abstract

The EGF receptor can bind seven different agonist ligands. Although each agonist appears to stimulate the same suite of downstream signaling proteins, different agonists are capable of inducing distinct responses in the same cell. To determine the basis for these differences, we used luciferase fragment complementation imaging to monitor the recruitment of Cbl, CrkL, Gab1, Grb2, PI3K, p52 Shc, p66 Shc, and Shp2 to the EGF receptor when stimulated by the seven EGF receptor ligands. Recruitment of all eight proteins was rapid, dose-dependent, and inhibited by erlotinib and lapatinib, although to differing extents. Comparison of the time course of recruitment of the eight proteins in response to a fixed concentration of each growth factor revealed differences among the growth factors that could contribute to their differing biological effects. Principal component analysis of the resulting data set confirmed that the recruitment of these proteins differed between agonists and also between different doses of the same agonist. Ensemble clustering of the overall response to the different growth factors suggests that these EGF receptor ligands fall into two major groups as follows: (i) EGF, amphiregulin, and EPR; and (ii) betacellulin,...Continue Reading

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Citations

Dec 24, 2017·Journal of Cellular Biochemistry·Jeongyeon HeoHara Kang
Mar 27, 2018·Developmental Neurobiology·Wei GuoBai Lu
Aug 17, 2018·Science Translational Medicine·William D ShipmanTheresa T Lu
Sep 17, 2016·F1000Research·Bhuminder SinghRobert J Coffey
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Oct 31, 2020·The Journal of Biological Chemistry·Kelly KarlKalina Hristova
Dec 19, 2020·International Journal of Molecular Sciences·Rebecca C FeinerKristian M Müller
Jan 18, 2021·The Journal of Biological Chemistry·Kelly KarlKalina Hristova

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