The AXL Receptor Is a Sensor of Ligand Spatial Heterogeneity
Name
The AXL receptor.pdf
Size
2.34 MB
Format
Adobe PDF
Checksum (MD5)
44553e163282f53455f837121c00df5a
Author(s)
Meyer, Aaron Samuel
Zweemer, Jacomina M.
Lauffenburger, Douglas A
Date Issued
July 2015
Journal
Cell Systems
Publisher
Elsevier
Citation
Meyer, Aaron S., Annelien J.M. Zweemer, and Douglas A. Lauffenburger. “The AXL Receptor Is a Sensor of Ligand Spatial Heterogeneity.” Cell Systems 1.1 (2015): 25–36.
Version
Author's final manuscript
Abstract
The AXL receptor is a TAM (Tyro3, AXL, MerTK) receptor tyrosine kinase (RTK) important in physiological inflammatory processes such as blood clotting, viral infection, and innate immune-mediated cell clearance. Overexpression of the receptor in a number of solid tumors is increasingly appreciated as a key drug resistance and tumor dissemination mechanism. Although the ligand-receptor (Gas6-AXL) complex structure is known, literature reports on ligand-mediated signaling have provided conflicting conclusions regarding the influence of other factors such as phosphatidylserine binding, and a detailed, mechanistic picture of AXL activation has not emerged. Integrating quantitative experiments with mathematical modeling, we show here that AXL operates to sense local spatial heterogeneity in ligand concentration, a feature consistent with its physiological role in inflammatory cell responses. This effect arises as a result of an intricate reaction-diffusion interaction. Our results demonstrate that AXL functions distinctly from other RTK families, a vital insight for the envisioned design of AXL-targeted therapeutic intervention.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cels.2015.06.002
