Topological control of cytokine receptor signaling induces differential effects in hematopoiesis-Reference-Cited by-同舟云学术

Topological control of cytokine receptor signaling induces differential effects in hematopoiesis

Published:2019-05-24 Issue:6442 Volume:364 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Mohan Kritika¹^ORCID,Ueda George²³^ORCID,Kim Ah Ram⁴⁵⁶^ORCID,Jude Kevin M.⁷^ORCID,Fallas Jorge A.²³^ORCID,Guo Yu⁸^ORCID,Hafer Maximillian⁹^ORCID,Miao Yi¹^ORCID,Saxton Robert A.¹⁷^ORCID,Piehler Jacob⁹¹⁰^ORCID,Sankaran Vijay G.⁴⁵⁶^ORCID,Baker David²³¹¹^ORCID,Garcia K. Christopher¹⁷¹²^ORCID

Affiliation:

1. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.

2. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

3. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.

4. Division of Hematology/Oncology, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

5. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

6. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

7. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

8. State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, People’s Republic of China.

9. Division of Biophysics, Department of Biology, University of Osnabrück, 49076 Osnabrück, Germany.

10. Center for Cellular Nanoanalytics, University of Osnabrück, 49076 Osnabrück, Germany.

11. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

12. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract

Exploring a range of signaling Cytokines are small proteins that bind to the extracellular domains of transmembrane receptors to activate signaling pathways inside the cell. They often act by dimerizing their receptors, and changes in dimer orientation of the extracellular domains can change the signaling output. Mohan et al. systematically explored this tuning effect by designing a series of dimer ligands for the erythropoietin receptor in which they varied the distance and angle between monomers. The topology affected the strength of activation and differentially affected different pathways, which raises the potential for exploiting such ligands in medicinal chemistry. Science , this issue p. eaav7532

Funder

National Institutes of Health

Howard Hughes Medical Institute

G Harold and Leila Y. Mathers Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference66 articles.

1. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases

2. Interpreting mixed signals: the cell's cytokine conundrum

3. Insights into Cytokine–Receptor Interactions from Cytokine Engineering