Early signaling dynamics of the epidermal growth factor receptor

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  • Raven J. Reddy
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Aaron S. Gajadhar
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Eric J. Swenson
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Daniel A. Rothenberg
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Timothy G. Curran
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Forest M. White
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;

Description

<jats:title>Significance</jats:title> <jats:p>To date, poor temporal resolution of response measurement has obscured the complex initiation of receptor tyrosine kinase (RTK) signaling that governs cellular response to stimulation. To address this deficiency, we have performed a systems-level characterization of the phosphorylation changes that occur in the immediate period after growth factor stimulation with 10-s resolution. We treated MCF-10A cells with EGF and measured tyrosine phosphorylation levels from 0 to 80 s on hundreds of sites in the cell. Examining phosphorylation dynamics on this timescale reveals patterns that were not observable with slower sampling rates. We further explore the roles of negative and positive feedback, providing further insight into systems-level behaviors of the EGF receptor (EGFR) signaling network.</jats:p>

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