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
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3T3 Cells
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Animals
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Base Sequence
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Line
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Cells, Cultured
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Chlorocebus aethiops
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Cloning, Molecular
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DNA Primers
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Drosophila melanogaster
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Endothelium, Vascular / metabolism*
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Humans
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Immunoglobulin Fc Fragments / biosynthesis
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Immunoglobulin Fc Fragments / metabolism
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Immunoglobulin G / biosynthesis
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Immunoglobulin G / metabolism
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Interleukin-1 / metabolism
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Interleukin-1 / pharmacology*
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-8 / biosynthesis
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Membrane Proteins*
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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Promoter Regions, Genetic
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Protein Biosynthesis
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Proteins / metabolism*
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Receptors, Cell Surface
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Receptors, Interleukin
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Receptors, Interleukin-1 / biosynthesis
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Receptors, Interleukin-1 / metabolism*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / metabolism
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Restriction Mapping
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Transfection
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Umbilical Veins
Substances
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DNA Primers
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IL1RL1 protein, human
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Il1rl1 protein, mouse
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Immunoglobulin Fc Fragments
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Immunoglobulin G
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Interleukin-1
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-8
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Membrane Proteins
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Proteins
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Receptors, Cell Surface
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Receptors, Interleukin
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Receptors, Interleukin-1
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Recombinant Fusion Proteins
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Calcium-Calmodulin-Dependent Protein Kinases