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Symmetric signaling by an asymmetric 1 erythropoietin : 2 erythropoietin receptor complex

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dc.contributor.advisor Harvey F. Lodish. en_US Zhang, Yingxin en_US
dc.contributor.other Massachusetts Institute of Technology. Biological Engineering Division. en_US 2009-04-29T17:08:54Z 2009-04-29T17:08:54Z 2008 en_US 2008 en_US
dc.description Thesis (M. Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008. en_US
dc.description Includes bibliographical references (p. 43-46). en_US
dc.description.abstract One erythropoietin molecule binds asymmetrically to two identical receptor monomers via erythropoietin site 1 and site 2, although it is unclear how asymmetry affects receptor activation and signaling. Here we report the computational design and experimental validation of two mutant erythropoietin receptors: one that binds only to erythropoietin site 1 but not site 2, and one that binds only to site 2 but not site 1. Expression of either mutant receptor alone in Ba/F3 cells cannot elicit a signal in response to erythropoietin, but when co-expressed, there is a proliferative response and activation of the JAK2 Stat5 signaling pathway. A truncated erythropoietin receptor with only one cytosolic tyrosine (Y343), on only one receptor monomer is sufficient for signaling in response to erythropoietin, regardless of the monomer on which it is located. The same results apply to having only one conserved juxtamembrane hydrophobic L253 or W258 residue, essential for JAK2 activation, in the full-length receptor dimer. We conclude that despite asymmetry in the ligand-receptor dimer interaction, both sides are competent for signaling, and we suggest that the receptors signal equally. en_US
dc.description.statementofresponsibility by Yingxin Zhang. en_US
dc.format.extent 46 p. en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri en_US
dc.subject Biological Engineering Division. en_US
dc.title Symmetric signaling by an asymmetric 1 erythropoietin : 2 erythropoietin receptor complex en_US
dc.type Thesis en_US M.Eng. en_US
dc.contributor.department Massachusetts Institute of Technology. Biological Engineering Division. en_US
dc.identifier.oclc 302346628 en_US

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