Symmetric Signaling by an Asymmetric 1 Erythropoietin: 2 Erythropoietin Receptor Complex
Name
Zhang-2009-Symmetric Signaling.pdf
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Author(s)
Zhang, Yingxin L.
Radhakrishnan, Mala L.
Lu, Xiaohui
Gross, Alec W.
Tidor, Bruce
Lodish, Harvey F
Date Issued
January 2009
Journal
Molecular Cell
Publisher
Elsevier
Citation
Zhang, Yingxin L., Mala L. Radhakrishnan, Xiaohui Lu, Alec W. Gross, Bruce Tidor, and Harvey F. Lodish. “Symmetric Signaling by an Asymmetric 1 Erythropoietin: 2 Erythropoietin Receptor Complex.” Molecular Cell 33, no. 2 (January 2009): 266–274. © 2009 Elsevier Inc.
Version
Final published version
Abstract
Via sites 1 and 2, erythropoietin binds asymmetrically to two identical receptor monomers, although it is unclear how asymmetry affects receptor activation and signaling. Here we report the design and validation of two mutant erythropoietin receptors that probe the role of individual members of the receptor dimer by selectively binding either site 1 or site 2 on erythropoietin. Ba/F3 cells expressing either mutant receptor do not respond to erythropoietin, but cells co-expressing both receptors respond to erythropoietin by proliferation and activation of the JAK2-Stat5 pathway. A truncated receptor with only one cytosolic tyrosine (Y343) is sufficient for signaling in response to erythropoietin, regardless of the monomer on which it is located. Similarly, only one receptor in the dimer needs a juxtamembrane hydrophobic L253 or W258 residue, essential for JAK2 activation. We conclude that despite asymmetry in the ligand-receptor interaction, both sides are competent for signaling, and appear to signal equally.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2008.11.026
