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

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 nee

SUBMITTER: Zhang YL 

PROVIDER: S-EPMC2706114 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature