Signaling via Src family kinases is required for normal internalization ofthe receptor c-Kit

Stem cell factor (SCF) exerts its biological effects by binding to a specif ic receptor, the tyrosine kinase c-Kit, which is expressed on the cell surf ace. Although normal cellular trafficking of growth factor receptors may pl ay a critical role in the modulation of receptor function, the mechanisms t hat regulate the distribution of c-Kit on the cell surface and the internal ization of c-Kit have not been fully defined. We investigated whether signa l transduction via Src family kinases is required for normal c-Kit traffick ing. Treatment of the SCF-responsive human hematopoietic cell line MO7e wit h 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-coate d pits occurs independently of Src family kinases, SCF-induced internalizat ion of c-Kit was also diminished in the D33-3 lymphoid cell line in which e xpression of Lyn kinase was disrupted by homologous recombination, These re sults indicate that Src family kinases play a role in ligand-induced traffi cking of c-Kit, (C) 1999 by The American Society of Hematology.