Department of Materials Science and Engineering, Institute for NanoBioTechnology, and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, MD 21218, United States.
Department of Materials Science and Engineering, Institute for NanoBioTechnology, and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, MD 21218, United States.
J Mol Biol. 2021 Jun 25;433(13):167006. doi: 10.1016/j.jmb.2021.167006. Epub 2021 Apr 20.
In this work, we put forward the provocative hypothesis that the active, ligand-bound RTK dimers from unrelated subfamilies can associate into heterooligomers with novel signaling properties. This hypothesis is based on a quantitative FRET study that monitors the interactions between EGFR and VEGFR2 in the plasma membrane of live cells in the absence of ligand, in the presence of either EGF or VEGF, and in the presence of both ligands. We show that direct interactions occur between EGFR and VEGFR2 in the absence of ligand and in the presence of the two cognate ligands. However, there are not significant heterointeractions between EGFR and VEGFR2 when only one of the ligands is present. Since RTK dimers and RTK oligomers are believed to signal differently, this finding suggests a novel mechanism for signal diversification.
在这项工作中,我们提出了一个有争议的假设,即来自不同亚家族的活性、配体结合的 RTK 二聚体可以与具有新信号特性的异源寡聚体结合。这个假设是基于一项定量 FRET 研究,该研究监测了在没有配体、存在 EGF 或 VEGF 以及存在两种配体的情况下,活细胞质膜中 EGFR 和 VEGFR2 之间的相互作用。我们表明,在没有配体和存在两种同源配体的情况下,EGFR 和 VEGFR2 之间会发生直接相互作用。然而,当只有一种配体存在时,EGFR 和 VEGFR2 之间没有显著的异源相互作用。由于 RTK 二聚体和 RTK 寡聚体被认为具有不同的信号传递方式,这一发现为信号多样化提供了一种新的机制。