Stem-cell factor receptor

H. Wu, U. Klingmuller, P. Besmer, and H. F. Lodish, Interaction of the erythropoietin and stem-cell-factor receptors, Nature Ml, 242-246 (1995). 

SCF (stromal or stem cell factor) receptor mostly known as cKit... 

Motesanib [31] (http //www.amgen.com/science/pipe.jsp) is an orally administered small molecule antagonist of VEGFRl-3, PDGFR, and stem cell factor receptor ( c-kit ). It is being investigated in phase 111 clinical trials as a first-line non-small cancer treatment. 

Growth factors, which are produced both as soluble and membrane-bound isotype proteins include members of the receptor tyrosine kinase subclass 111, such as stem cell factor (SCF) (Anderson et al, 1990 Huang et al, 1990), colony stimulating factor-1 (CSF-1, M-CSF) (Ladner et al, 1988 Ceretti et al, 1988) and Fit 3 ligand (Hannum et al, 1994 McClanahan et al, 1996). 

Zsebo KM, Williams DA, Geissler EN, Broudy VC, Martin FH, Atkins HL, Hsu R Y, Birkett NC, Okino KH, Mmdock DC, Jacobsen FW, Langley KE, Smith KA, Takeishi T, Cattanach BM, Galli SJ, Suggs SV, 1990. Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c kit tyrosine kinase receptor. Cell 63 213... 

Although Gleevec was carefully designed to inhibit the specific tyrosine kinase produced by the Philadelphia chromosome, it also produces unexpected activities. Gleevec blocks c-kit (the receptor for stem cell factor) [40], and the receptor for platelet-derived growth factor [41]. These additional activities could result in a broader array of antitumor activities, in a broader spectrum of toxicities, or both [42]. 

Imatinib (STI571) is an inhibitor of the tyrosine kinase domain of the Bcr-Abl oncoprotein and prevents the phosphorylation of the kinase substrate by ATP. It is indicated for the treatment of chronic myelogenous leukemia (CML), a pluripotent hematopoietic stem cell disorder characterized by the t(9 22) Philadelphia chromosomal translocation. This translocation results in the Bcr-Abl fusion protein, the causative agent in CML, and is present in up to 95% of patients with this disease. This agent inhibits other activated receptor tyrosine kinases for platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF), and c-kit. 

Stem cell factor, SCF, also called steel factor or mast cell growth factor is a cytokine that stimulates the proliferation of myeloid and lymphoid hemopoietic progenitor cells. SCF is a ligand of the receptor tyrosine kinase, c-KIT, a protoonct ene. The KIT oncogene is the gene of a transforming feline sarcoma virus. 

Stem cell factor (SCF) is a dimeric protein that stimulates hematopoietic progenitor cells in bone marrow. The interaction of SCF expressed in E. coli and its receptor, soluble Kit (sKit), was studied (5). The extinction coefficient of the SCF was obtained as 0.534 by using Gill s amino acid composition method and 0.585 by using the method described in this paper [note 0.62 ml/(mg-cm) was reported in reference 11 by the amino acid analysis method]. In this complicated case, a self-consistent three-detector method described in reference 2 was used to determine the stoichiometry of the complex. The results of using these two extinction coefficients are summarized in tables IIIA and IIIB. Both results indicate that the stem cell factor dimerizes its receptor, sKit. 

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