ST2/T1 PROTEIN FUNCTIONALLY BINDS TO 2 SECRETED PROTEINS FROM BALB/C 3T3 AND HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS BUT DOES NOT BIND INTERLEUKIN-1

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-g promoter reporter gene that was cotransfected into Jurkat cells with a full-length IL-IR 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-IRI 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 RAP kinase through the ST2 receptor, These results suggest that the ST2 is not an IL-1 receptor but rather has its own cognate ligand.