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

@article{citeulike:2792223, abstract = {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. 10.1126/science.1154370}, author = {Lin, Haishan and Lee, Ernestine and Hestir, Kevin and Leo, Cindy and Huang, Minmei and Bosch, Elizabeth and Halenbeck, Robert and Wu, Ge and Zhou, Aileen and Behrens, Dirk and Hollenbaugh, Diane and Linnemann, Thomas and Qin, Minmin and Wong, Justin and Chu, Keting and Doberstein, Stephen K. and Williams, Lewis T. }, citeulike-article-id = {2792223}, doi = {10.1126/science.1154370}, journal = {Science}, keywords = {cytokine, method, proteomics}, month = {May}, number = {5877}, pages = {807--811}, posted-at = {2008-05-13 02:59:43}, priority = {2}, title = {Discovery of a Cytokine and Its Receptor by Functional Screening of the Extracellular Proteome}, url = {http://dx.doi.org/10.1126/science.1154370}, volume = {320}, year = {2008} }

TY - JOUR ID - citeulike:2792223 L3 - citeulike-article-id:2792223 TI - Discovery of a Cytokine and Its Receptor by Functional Screening of the Extracellular Proteome JF - Science VL - 320 IS - 5877 SP - 807 EP - 811 N2 - 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. 10.1126/science.1154370 KW - cytokine KW - method KW - proteomics AU - Lin, Haishan AU - Lee, Ernestine AU - Hestir, Kevin AU - Leo, Cindy AU - Huang, Minmei AU - Bosch, Elizabeth AU - Halenbeck, Robert AU - Wu, Ge AU - Zhou, Aileen AU - Behrens, Dirk AU - Hollenbaugh, Diane AU - Linnemann, Thomas AU - Qin, Minmin AU - Wong, Justin AU - Chu, Keting AU - Doberstein, Stephen AU - Williams, Lewis PY - 2008/05/09/ UR - http://dx.doi.org/10.1126/science.1154370 ER -