MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Symmetric Signaling by an Asymmetric 1 Erythropoietin: 2 Erythropoietin Receptor Complex

Author(s)
Zhang, Yingxin L.; Radhakrishnan, Mala L.; Lu, Xiaohui; Gross, Alec W.; Tidor, Bruce; Lodish, Harvey F; ... Show more Show less
Thumbnail
DownloadZhang-2009-Symmetric Signaling.pdf (1016.Kb)
PUBLISHER_POLICY

Publisher Policy

Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.

Terms of use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Metadata
Show full item record
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.
Date issued
2009-01
URI
http://hdl.handle.net/1721.1/96330
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
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
ISSN
10972765
1097-4164

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.