title: ST2/T1 protein functionally binds to two secreted proteins from Balb/c 3T3 and human umbilical vein endothelial cells but does not bind interleukin 1.
abstract: The ST2/T1 receptor, a homologue of the interleukin 1 receptor (IL-1R), was expressed in COS and Drosophila S2 cells as a human IgG-Fc fusion protein. While a type I IL-1RFc fusion protein bound human IL-1 in vitro, the ST2Fc fusion protein did not. Furthermore, IL-1 stimulated a synthetic interleukin-8 promoter reporter gene that was cotransfected into Jurkat cells with a full-length IL-1R type I (IL-1RI) or a chimeric receptor composed of the IL-1RI extracellular domain and ST2 intracellular domain. In contrast, IL-1 did not stimulate the interleukin-8 promoter when cotransfected with a full-length ST2 or an ST2 extracellular/IL-1R intracellular domain fusion protein. Both IL-1RI and the IL-1R/ST2R chimeric receptor also activated a receptor-associated kinase and CSBP/p38 MAP kinase. Using ST2Fc receptor, we have identified, through receptor precipitation, receptor-dot blot and surface plasmon resonance, a putative ligand of ST2 secreted from Balb/c 3T3 and human umbilical vein endothelial cells. The putative ligand was also able to stimulate CSBP/p38 MAP kinase through the ST2 receptor. These results suggest that the ST2 is not an IL-1 receptor but rather has its own cognate ligand.
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017931:DNA Primers; D004331:Drosophila melanogaster; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000096:biosynthesis / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016209:Interleukin-8 / Q000096:biosynthesis; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D014162:Transfection; D014471:Umbilical Veins
chemical_list: D017931:DNA Primers; C079241:IL1RL1 protein, human; C486189:Il1rl1 protein, mouse; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007375:Interleukin-1; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016209:Interleukin-8; D008565:Membrane Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases