• DOI:10.1126/science.1154370
• Corpus ID: 44340470

Discovery of a Cytokine and Its Receptor by Functional Screening of the Extracellular Proteome

@article{Lin2008DiscoveryOA,
  title={Discovery of a Cytokine and Its Receptor by Functional Screening of the Extracellular Proteome},
  author={Haishan Lin and Ernestine Lee and Kevin Hestir and Cindy Leo and Minmei Huang and Elizabeth Bosch and Robert F. Halenbeck and Ge Wu and Aileen J Zhou and Dirk Behrens and Diane L Hollenbaugh and Thomas Linnemann and Minmin Qin and Justin Jong-Leong Wong and Keting Emeryville Chu and Stephen. Doberstein and Lewis T. Williams},
  journal={Science},
  year={2008},
  volume={320},
  pages={807 - 811}
}

• Haishan Lin, Ernestine Lee, +14 authors L. Williams
• Published 9 May 2008
• Biology
• Science

To understand the system of secreted proteins and receptors involved in cell-cell signaling, we produced a comprehensive set of recombinant secreted proteins and the extracellular domains of transmembrane proteins, which constitute most of the protein components of the extracellular space. Each protein was tested in a suite of assays that measured metabolic, growth, or transcriptional responses in diverse cell types. The pattern of responses across assays was analyzed for the degree of functional selectivity of each protein. One of the highly selective proteins was a previously undescribed ligand, designated interleukin-34 (IL-34), which stimulates monocyte viability but does not affect responses in a wide spectrum of other assays. In a separate functional screen, we used a collection of extracellular domains of transmembrane proteins to discover the receptor for IL-34, which was a known cytokine receptor, colony-stimulating factor 1 (also called macrophage colony-stimulating factor) receptor. This systematic approach is thus useful for discovering new ligands and receptors and assessing the functional selectivity of extracellular regulatory proteins.