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dc.contributor.authorZhang, Yingxin L.
dc.contributor.authorRadhakrishnan, Mala L.
dc.contributor.authorLu, Xiaohui
dc.contributor.authorGross, Alec W.
dc.contributor.authorTidor, Bruce
dc.contributor.authorLodish, Harvey F
dc.date.accessioned2015-04-02T16:30:00Z
dc.date.available2015-04-02T16:30:00Z
dc.date.issued2009-01
dc.date.submitted2008-09
dc.identifier.issn10972765
dc.identifier.issn1097-4164
dc.identifier.urihttp://hdl.handle.net/1721.1/96330
dc.description.abstractVia 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.sponsorshipNational Institutes of Health (U.S.) (Grant P01 HL32262)en_US
dc.description.sponsorshipAmgen Inc. (Research Grant)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant GM 065418)en_US
dc.description.sponsorshipUnited States. Dept. of Energy. Computational Science Graduate Fellowship (DE-FG02-97ER25308)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (Postdoctoral Fellowship 5F32HL077036)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.molcel.2008.11.026en_US
dc.rightsArticle 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.sourceElsevieren_US
dc.titleSymmetric Signaling by an Asymmetric 1 Erythropoietin: 2 Erythropoietin Receptor Complexen_US
dc.typeArticleen_US
dc.identifier.citationZhang, 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.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Scienceen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorZhang, Yingxin L.en_US
dc.contributor.mitauthorRadhakrishnan, Mala L.en_US
dc.contributor.mitauthorLu, Xiaohuien_US
dc.contributor.mitauthorGross, Alec W.en_US
dc.contributor.mitauthorTidor, Bruceen_US
dc.contributor.mitauthorLodish, Harvey F.en_US
dc.relation.journalMolecular Cellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsZhang, Yingxin L.; Radhakrishnan, Mala L.; Lu, Xiaohui; Gross, Alec W.; Tidor, Bruce; Lodish, Harvey F.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-3320-3969
dc.identifier.orcidhttps://orcid.org/0000-0002-7029-7415
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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