Instructive roles for cytokine-receptor binding parameters in determining signaling and functional potency.

ABSTRACT: Cytokines dimerize cell surface receptors to activate signaling and regulate many facets of the immune response. Many cytokines have pleiotropic effects, inducing a spectrum of redundant and distinct effects on different cell types. This pleiotropy has hampered cytokine-based therapies, and the high doses required for treatment often lead to off-target effects, highlighting the need for a more detailed understanding of the parameters controlling cytokine-induced signaling and bioactivities. Using the prototypical cytokine interleukin-13 (IL-13), we explored the interrelationships between receptor binding and a wide range of downstream cellular responses. We applied structure-based engineering to generate IL-13 variants that covered a spectrum of binding strengths for the receptor subunit I

SUBMITTER: Moraga I 

PROVIDER: S-EPMC5568809 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature