Signaling via Src family kinases is required for normal internalization of the receptor c-Kit.

Stem cell factor (SCF) exerts its biological effects by binding to a specific receptor, the tyrosine kinase c-Kit, which is expressed on the cell surface. Although normal cellular trafficking of growth factor receptors may play a critical role in the modulation of receptor function, the mechanisms that regulate the distribution ...
of c-Kit on the cell surface and the internalization of c-Kit have not been fully defined. We investigated whether signal transduction via Src family kinases is required for normal c-Kit trafficking. Treatment of the SCF-responsive human hematopoietic cell line MO7e with the inhibitor of Src family kinases PP1 blocked SCF-induced capping of c-Kit and internalization of c-Kit. c-Kit was able to associate with clathrin in the presence of PP1, suggesting that entry of c-Kit into clathrin-coated pits occurs independently of Src family kinases. SCF-induced internalization of c-Kit was also diminished in the D33-3 lymphoid cell line in which expression of Lyn kinase was disrupted by homologous recombination. These results indicate that Src family kinases play a role in ligand-induced trafficking of c-Kit.
Mesh Terms:
Cell Membrane, Chemotaxis, Clathrin, Coated Pits, Cell-Membrane, Gene Expression Regulation, Enzymologic, Humans, Kinetics, Leukemia, Proto-Oncogene Proteins c-kit, Pyrazoles, Pyrimidines, Recombination, Genetic, Signal Transduction, Stem Cell Factor, Tumor Cells, Cultured, src-Family Kinases
Blood
Date: Sep. 15, 1999
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