Cytokine signaling as a cascade of protein interactions for multiple outputs

How do similar ligands binding to the same receptor complex trigger diverse biological activities such as antiviral, antiproliferative, and immunomodulatory effects? To explore this phenomenon, we adopted a biophysical and cellular approach that delves into the detailed examination of different system components individually and within the complexity of the cellular environment.

Our approach encompasses the following strategies: Structure/function analyses of the ligand-receptor complex.

  • Building a comprehensive set of interferon and interferon receptor mutants as well as numerous cell lines with systematic modifications or deletions of genes involved in the interferon signaling pathway. Utilizing gene arrays and high-resolution molecular techniques to investigate how variations in system components affect differential signaling pathways. Our findings suggest that differential activation can be attributed to the biophysical properties of binding and activation within the system. Essentially, the intricate cellular behavior is governed by biophysical principles, including the affinity, abundance, localization, and competition among the various system components.