@article{e65ae6fb44494b6fb6b22066ecfb7f79,
title = "Competition for shared downstream signaling molecules establishes indirect negative feedback between EGFR and EphA2",
abstract = "Cells sense a variety of extracellular growth factors and signaling molecules through numerous distinct receptor tyrosine kinases (RTKs) on the cell surface. In many cases, the same intracellular signaling molecules interact with more than one type of RTK. How signals from different RTKs retain the identity of the triggering receptor and how (or if) different receptors may synergize or compete remain largely unknown. Here we utilize an experimental strategy, combining microscale patterning and single-molecule imaging, to measure the competition between ephrin-A1:EphA2 and epidermal growth factor (EGF):EGF receptor (EGFR) ligand-receptor complexes for the shared downstream signaling molecules, Grb2 and SOS. The results reveal a distinct hierarchy, in which newly formed EGF:EGFR complexes outcompete ephrin-A1:EphA2 for Grb2 and SOS, revealing a type of negative crosstalk interaction fundamentally controlled by chemical mass action and protein copy number limitations.",
author = "Dongmyung Oh and Zhongwen Chen and Biswas, {Kabir H.} and Funing Bai and Ong, {Hui Ting} and Sheetz, {Michael P.} and Groves, {Jay T.}",
note = "Funding Information: We thank Adrienne Greene (J.T.G.{\textquoteright}s laboratory, University of California, Berkeley) for her contribution of purified ephrin-A1 proteins, as well as helpful discussions. We thank Jean K. Jung for helping in SLB substrate hybridization. We thank members in J.T.G.{\textquoteright}s laboratory and M.P.S.{\textquoteright}s laboratory for stimulating discussions and sharing of reagents. This work was supported by the Novo Nordisk Foundation Challenge Program under the Center for Geometrically Engineered Cellular Systems. Collaborative work at the Mechanobiology Institute, National University of Singapore, was supported by CRP001-084. Z.C. is funded by Shanghai Municipal Science and Technology Major Project ZJLab (2019SHZDZX02). Funding Information: We thank Adrienne Greene (J.T.G.{\textquoteright}s laboratory, University of California, Berkeley) for her contribution of purified ephrin-A1 proteins, as well as helpful discussions. We thank Jean K. Jung for helping in SLB substrate hybridization. We thank members in J.T.G.{\textquoteright}s laboratory and M.P.S.{\textquoteright}s laboratory for stimulating discussions and sharing of reagents. This work was supported by the Novo Nordisk Foundation Challenge Program under the Center for Geometrically Engineered Cellular Systems. Collaborative work at the Mechanobiology Institute , National University of Singapore , was supported by CRP001-084 . Z.C. is funded by Shanghai Municipal Science and Technology Major Project ZJLab ( 2019SHZDZX02 ). Publisher Copyright: {\textcopyright} 2022",
year = "2022",
month = may,
day = "17",
doi = "10.1016/j.bpj.2022.04.015",
language = "English (US)",
volume = "121",
pages = "1897--1908",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "10",
}