The ST2 gene, also known as T1, Fit1, or DER4, was originally identified as a responsive gene that was highly induced by stimulation of various proliferation-inducing agents including serum, PDGF (platelet-derived growth factor), FGF (fibroblast growth factor), or lysophosphatidic acid in murine fibroblasts. Three distinct forms of gene products have been reported and named ST2, ST2V, and ST2L. ST2 is a soluble secreted form of 37 kDa protein, which lacks intracellular domain, whereas ST2L is a transmembrane form of 62 kDa protein (the glycosylated forms of ST2 and ST2L are about 57 and 80 kDa, respectively). This ST2L protein is very similar to IL-1R (interleukin-1 receptor) type I and II in structure, thus it is considered as a member of the IL-1R family. ST2V, which is another novel variant form of human ST2, has been identified recently. ST2 proteins are expressed in the wide variety types of human cells, including hematopoietic cells in various stages of differentiation, a population of the peripheral blood mononuclear cells from healthy individuals, glioblastoma and astrocytoma cell lines, and colon cancer cells in addition to fibroblast cell lines. Thus ST2 proteins are considered to have some roles in regulating cell growth or proliferation. On the other hand, either definitive functions of ST2 proteins or their ligand molecule(s) which binds to ST2 proteins have remained unclear, though it has been reported that none of IL-1?, ?, RA (receptor antagonist) binds to ST2 proteins in spite of their structural similarity to IL-1R. This indicates that ST2L protein is functionally independent from IL-1R. Furthermore, several studies have shown that ST2L is expressed on the cell surface of Th2 cells but not on the Th1 cells, indicating the possibility that ST2L protein participates not only in the regulation of cell growth or proliferation, but also in the immune system including differentiation of T cells or immunological response via helper T cells. From these observations, ST2 proteins are considered to be one of the important proteins participate in various physiological phenomenon, thus further analysis are required to understand its physiological functions.
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