Erythropoietin receptor activation by a ligand-induced conformation change

Erythropoietin and other cytokine receptors are thought to be activated thr ough hormone-induced dimerization and autophosphorylation of JAK kinases as sociated with the receptor intracellular domains, An in vivo protein fragme nt complementation assay was used to obtain evidence for an alternative mec hanism in which unliganded erythropoietin receptor dimers exist in a confor mation that prevents activation of JAK2 but then undergo a ligand-induced c onformation change that allows JAK2 to be activated, These results are cons istent with crystallographic evidence of distinct dimeric configurations fo r unliganded and ligand-bound forms of the erythropoietin receptor.