Transmembrane Protein Aptamer Induces Cooperative Signaling by the EPO Receptor and the Cytokine Receptor β-Common Subunit

Li He; Emily B. Cohen; Anne P.B. Edwards; Juliana Xavier-Ferrucio; Katrine Bugge; Ross S. Federman; Devin Absher; Richard M. Myers; Birthe B. Kragelund; Diane S. Krause; Daniel DiMaio

iScience (Jul 2019)

Transmembrane Protein Aptamer Induces Cooperative Signaling by the EPO Receptor and the Cytokine Receptor β-Common Subunit

Li He,
Emily B. Cohen,
Anne P.B. Edwards,
Juliana Xavier-Ferrucio,
Katrine Bugge,
Ross S. Federman,
Devin Absher,
Richard M. Myers,
Birthe B. Kragelund,
Diane S. Krause,
Daniel DiMaio

Affiliations

Li He: Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005, USA
Emily B. Cohen: Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005, USA
Anne P.B. Edwards: Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005, USA
Juliana Xavier-Ferrucio: Department of Laboratory Medicine, Yale School of Medicine, P.O. Box 208073, New Haven, CT 06520-8073, USA
Katrine Bugge: Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and Integrative Structural Biology at University of Copenhagen (ISBUC), Department of Biology, University of Copenhagen, Copenhagen N 2200, Denmark
Ross S. Federman: Department of Immunobiology, Yale School of Medicine, P.O. Box 208011, New Haven, CT 06520-8011, USA
Devin Absher: HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA
Richard M. Myers: HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA
Birthe B. Kragelund: Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and Integrative Structural Biology at University of Copenhagen (ISBUC), Department of Biology, University of Copenhagen, Copenhagen N 2200, Denmark
Diane S. Krause: Department of Laboratory Medicine, Yale School of Medicine, P.O. Box 208073, New Haven, CT 06520-8073, USA; Yale Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028, USA
Daniel DiMaio: Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005, USA; Department of Therapeutic Radiology, Yale School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040, USA; Department of Molecular Biophysics & Biochemistry, P.O. Box 208114, Yale University, New Haven, CT 06520-8114, USA; Yale Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028, USA; Corresponding author

Journal volume & issue: Vol. 17
pp. 167 – 181

Abstract

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Summary: The erythropoietin receptor (EPOR) plays an essential role in erythropoiesis and other cellular processes by forming distinct signaling complexes composed of EPOR homodimers or hetero-oligomers between the EPOR and another receptor, but the mechanism of heteroreceptor assembly and signaling is poorly understood. We report here a 46-residue, artificial transmembrane protein aptamer, designated ELI-3, that binds and activates the EPOR and induces growth factor independence in murine BaF3 cells expressing the EPOR. ELI-3 requires the transmembrane domain and JAK2-binding sites of the EPOR for activity, but not the cytoplasmic tyrosines that mediate canonical EPOR signaling. Instead, ELI-3-induced proliferation and activation of JAK/STAT signaling requires the transmembrane and cytoplasmic domains of the cytokine receptor β-common subunit (βcR) in addition to the EPOR. Moreover, ELI-3 fails to induce erythroid differentiation of primary human hematopoietic progenitor cells but inhibits nonhematopoietic cell death induced by serum withdrawal. : Biological Sciences; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Biological Sciences, Cell Biology, Functional Aspects of Cell Biology

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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