The protooncogene c-kit and c-kit ligand in human disease☆,☆☆,★
Section snippets
SCF and c-kit function
The functions of c-kit and SCF, as studies performed on W and Sl mutant mice indicate, are interrelated. SCF, whether soluble or membrane-bound on stroma cells, fibroblasts, or endothelial cells, affects the differentiation and function of mast cells, hematopoietic progenitor cells, germ cells, and melanocytes through its interaction with the c-kit receptor. Defects in either gene in mice lead to a phenotype characterized by mast cell deficiency, macrocytic anemia, sterility, and lack of hair
Signal transduction after c-kit activation
Binding of SCF to membrane c-kit leads to receptor dimerization, transphosphorylation, and protein tyrosine kinase activation (Fig. 2).
c-kit disease association in human beings
Two states have been shown to be clearly associated with c-kit dysfunction in human beings. There is limited evidence that c-kit and SCF may be important in the pathogenesis of additional diseases.
Therapeutic use of SCF
Recently, the potential for therapeutic use of SCF has been explored. In particular, SCF has been used combined with chemotherapy to increase the mobilization of hematopoietic progenitor cells and shorten the period of pancytopenia after chemotherapy. Studies have been reported in which SCF was used in dose-intensive chemotherapeutic regimens in the treatment of patients with non-small cell lung cancer or breast cancer. SCF has demonstrated promising biologic activity in expanding the
References (11)
- et al.
Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines
Blood
(1995) - et al.
Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI–cell population
Blood
(1994) - et al.
Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c-kit receptor tyrosine kinase
Blood
(1996) - et al.
Steel factor and c-kit protooncogene: genetic lessons in signal transduction
Crit Rev Oncog
(1994) - et al.
Genetic disorders of pigmentation
Adv Hum Genet
(1994)
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The suppressive effect of dabrafenib, a therapeutic agent for metastatic melanoma, in IgE-mediated allergic inflammation
2020, International ImmunopharmacologyMelanocytes: A window into the nervous system
2012, Journal of Investigative DermatologyCitation Excerpt :Similarly, Steel factor and c-Kit are required for the development of the sensory nervous system (Zhang and Sieber-Blum, 2009). Piebaldism is an autosomal dominant disorder that results from mutations of c-Kit or steel factor and leads to failure of precursor melanocytes to migrate to the skin and survive there (Spritz, 1997; Vliagoftis et al., 1997). Affected individuals display broad depigmented patches, most prominent on the central forehead and trunk.
Identification of novel c-Kit inhibitors from natural sources using virtual screening and molecular dynamics simulations
2023, Journal of Biomolecular Structure and Dynamics
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From Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
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Reprint requests: Harissios Vliagoftis, MD, Laboratory of Allergic Diseases, NIAID, NIH, Bldg. 10, Rm 11C205, 10 Center Dr. MSC 1881, Bethesda, MD 20892-1881.
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