dc.contributor.author | Zhang, Yingxin L. | |
dc.contributor.author | Radhakrishnan, Mala L. | |
dc.contributor.author | Lu, Xiaohui | |
dc.contributor.author | Gross, Alec W. | |
dc.contributor.author | Tidor, Bruce | |
dc.contributor.author | Lodish, Harvey F | |
dc.date.accessioned | 2015-04-02T16:30:00Z | |
dc.date.available | 2015-04-02T16:30:00Z | |
dc.date.issued | 2009-01 | |
dc.date.submitted | 2008-09 | |
dc.identifier.issn | 10972765 | |
dc.identifier.issn | 1097-4164 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/96330 | |
dc.description.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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant P01 HL32262) | en_US |
dc.description.sponsorship | Amgen Inc. (Research Grant) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant GM 065418) | en_US |
dc.description.sponsorship | United States. Dept. of Energy. Computational Science Graduate Fellowship (DE-FG02-97ER25308) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (Postdoctoral Fellowship 5F32HL077036) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.molcel.2008.11.026 | en_US |
dc.rights | 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. | en_US |
dc.source | Elsevier | en_US |
dc.title | Symmetric Signaling by an Asymmetric 1 Erythropoietin: 2 Erythropoietin Receptor Complex | en_US |
dc.type | Article | en_US |
dc.identifier.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. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.mitauthor | Zhang, Yingxin L. | en_US |
dc.contributor.mitauthor | Radhakrishnan, Mala L. | en_US |
dc.contributor.mitauthor | Lu, Xiaohui | en_US |
dc.contributor.mitauthor | Gross, Alec W. | en_US |
dc.contributor.mitauthor | Tidor, Bruce | en_US |
dc.contributor.mitauthor | Lodish, Harvey F. | en_US |
dc.relation.journal | Molecular Cell | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Zhang, Yingxin L.; Radhakrishnan, Mala L.; Lu, Xiaohui; Gross, Alec W.; Tidor, Bruce; Lodish, Harvey F. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-3320-3969 | |
dc.identifier.orcid | https://orcid.org/0000-0002-7029-7415 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |