The protooncogene c-kit and c-kit ligand in human disease,☆☆,

https://doi.org/10.1016/S0091-6749(97)70131-3Get rights and content

Abstract

J Allergy Clin Immunol 1997;100:435-40.

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).

. Diagram of signal transduction pathways initiated through c-kit. Binding of SCF on cell membrane c-kit leads to dimerization of c-kit and transphosphorylation of tyrosine residues. Subsequent events lead to gene transcription, cell adhesion, and proliferation. PLCγ, Phospholipase Cγ; PI3K, phosphoinositol-3-kinase; PTP1C, protein tyrosine phosphatase 1 C; MAPKK,

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)

There are more references available in the full text version of this article.

Cited by (121)

  • Melanocytes: A window into the nervous system

    2012, Journal of Investigative Dermatology
    Citation 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.

View all citing articles on Scopus

From Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.

☆☆

Reprint requests: Harissios Vliagoftis, MD, Laboratory of Allergic Diseases, NIAID, NIH, Bldg. 10, Rm 11C205, 10 Center Dr. MSC 1881, Bethesda, MD 20892-1881.

1/1/84529

View full text