The Steel Factor/kit Ligand/Stem Cell Factor
Publisher Summary The human gene encoding the Steel factor is localized in the human chromosome 12q22–24—a region that is syntenic with the corresponding region of the mouse chromosome 10. The cloned Steel-factor gene encodes a transmembrane protein that undergoes proteolytic cleavage to generate a soluble form of the protein. The Steel-factor protein can undergo cleavage at either of the two alanine residues 164 or 165 that are found within the extracellular domain of the protein to generate a soluble form of the protein that is biologically active. The human protein contains 273 amino acids (aa), and the first 25 of these aa constitute a signal peptide that is removed in the mature protein. As a transmembrane protein, the Steel factor is biologically active on the cell surface. Its cysteine residues form two intramolecular disulfide bonds that establish the three-dimensional structure of the protein. The mature Steel-factor protein encodes a 248-aa transmembrane protein that undergoes proteolytic cleavage to generate a soluble form of the protein that is 164–165 aa long and biologically active. The expression of Steel factor and/or its receptor has been shown to result in the autocrine growth of a large number of various tumor types such as neuroblastoma, testicular tumors, hemangioma, small-cell lung tumors, and melanocytic tumors. The Steel factor been shown to increase the survival of malignant hematopoietic cells as well as protect the leukemic cells from chemotherapy and tumor cells from radiotherapy.