The role of tyrosine 15 in erythropoietin action.

The results of iodination inactivation of erythropoietin suggest that tyrosine 15 is required for biological activity. This was confirmed by site-directed mutagenesis. Substitution of tyrosine by alanine or isoleucine resulted in mutants with no biological activity, whereas substitution by phenylalanine yielded an active mutein. Protein footprinting using trypsin showed that the N-terminal residues 1 to 46 and the C-terminal residues 155 to 165 linked by the 7 to 161 disulfide bond, includes one active site of the hormone.