Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation

@article{Kim2017FunctionalSI,
  title={Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation},
  author={Ah Ram Kim and Jacob C. Ulirsch and Stephan Wilmes and Ekrem Unal and Ignacio Moraga and Musa Karakukcu and Daniel Yuan and Shideh Kazerounian and Nour J. Abdulhay and D. King and Namrata Gupta and Stacey Bolk Gabriel and Eric S. Lander and Turkan Patiroğlu and Alper Ozcan and Mehmet Akif Ozdemir and K Christopher Garcia and Jacob Piehler and Hanna T. Gazda and Daryl E. Klein and Vijay G Sankaran},
  journal={Cell},
  year={2017},
  volume={168},
  pages={1053-1064.e15}
}
Cytokines are classically thought to stimulate downstream signaling pathways through monotonic activation of receptors. We describe a severe anemia resulting from a homozygous mutation (R150Q) in the cytokine erythropoietin (EPO). Surprisingly, the EPO R150Q mutant shows only a mild reduction in affinity for its receptor but has altered binding kinetics. The EPO mutant is less effective at stimulating erythroid cell proliferation and differentiation, even at maximally potent concentrations… CONTINUE READING
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