Homodimerization and constitutuve activation of the erythropoietin receptor

A substitution of arginine-129 to cysteine in the erythropoietin receptor (EPO-R) results in a constitutively active signal transducing receptor. Because of its oncogenic significance, the mutation leading to the constututive EPO-R was characterized biochemically and mutagenically. The results showed that the presence of cysteine, and not the absence of arginine at position 129, leads to the constitutive phenotype. Furthermore, cysteine substitution leads to the formation of disulfide-linked homodimers, a fraction of which are transported to the plasma membrane. The results suggest that dimerization mimics the ligand-induced signal transduction