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Abstract

The EGF receptor will bind seven totally different agonist ligands. Though every agonist seems to stimulate constant suite of downstream communication proteins, totally different agonist’s are capable of causing distinct responses within the same cell. To work out the premise for these variations, we have a tendency to used luciferase fragment complementation imaging to observe the enlisting of Cbl, CrkL, Gab1, Grb2, PI3K, p52 Shc, p66 Shc, and Shp2 to the EGF receptor once stirred up by the seven EGF receptor ligands. Enlisting of all eight proteins was fast, dose-dependent, and repressed by erlotinib and lapatinib, though to differing extents. Comparison of the time course of enlisting of the eight proteins in response to a hard and fast concentration of every protein discovered variations among the expansion factors that might contribute to their differing biological effects. Principal element analysis of the ensuing information set confirmed that the enlisting of those proteins differed between agonists and conjointly between totally different doses of constant agonist. Ensemble agglomeration of the general response to the various growth factors suggests that these EGF receptor ligands be 2 major teams as follows: (i) EGF, amphiregulin, and EPR; and (ii) betacellulin, TGFα, and epigen. Heparin-binding EGF is distantly associated with each cluster. Our information establish variations in network utilization by totally different EGF receptor agonists and highlight the requirement to characterize network interactions beneath conditions apart from high dose EGF [1]