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.
Broudy
V C
VC
Divisions of Hematology, Department of Medicine, University of Washington, Seattle, WA, USA. vcbroudy@u.washington.edu
Lin
N L
NL
Liles
W C
WC
Corey
S J
SJ
O'Laughlin
B
B
Mou
S
S
Linnekin
D
D
D002462:Cell Membrane / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D002966:Clathrin / Q000378:metabolism; D003034:Coated Pits, Cell-Membrane / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007700:Kinetics; D007938:Leukemia; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011995:Recombination, Genetic; D015398:Signal Transduction / Q000502:physiology*; D019089:Stem Cell Factor / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D002966:Clathrin; D011720:Pyrazoles; D011743:Pyrimidines; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D019061:src-Family Kinases