Tyrosine kinase-deficient Wv c-kit induces mast cell adhesion and chemotaxis.
W/Wv mice are deficient in tissue mast cells, and mast cells cultured from these mice do not proliferate in response to the c-kit ligand, stem cell factor (SCF). In this paper, we report that mouse bone marrow cultured mast cells derived from W/Wv mice do adhere to fibronectin in the presence of SCF and exhibit chemotaxis to SCF, and we explore this model for the understanding of c-kit-mediated signaling pathways. Both in vitro and in vivo (in intact cells) phosphorylation experiments demonstrated a low residual level of W/Wv c-kit protein phosphorylation. SCF-induced responses in W/Wv mast cells were abolished by the tyrosine kinase inhibitor herbimycin A and by the phospatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin but were not affected by protein kinase C inhibitors. These observations are consistent with the conclusions that Wv c-kit initiates a signaling process that is PI 3-kinase dependent and that mutated Wv c-kit retains the ability to initiate mast cell adhesion and migration.
Dastych
J
J
Department of Biogenic Amines, Polish Academy of Sciences, 90-950 Lodz, Poland.
Taub
D
D
Hardison
M C
MC
Metcalfe
D D
DD
D000470:Alkaloids; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines; D016227:Benzoquinones; D001854:Bone Marrow Cells / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D047029:Lactams, Macrocyclic; D008301:Maleimides / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D010617:Phenanthridines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000494:pharmacology* / Q000502:physiology; D000077191:Wortmannin
D000470:Alkaloids; D000730:Androstadienes; D053119:Benzophenanthridines; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D007211:Indoles; D047029:Lactams, Macrocyclic; D008301:Maleimides; D010617:Phenanthridines; D011809:Quinones; D019089:Stem Cell Factor; D017828:Rifabutin; C020754:herbimycin; C016299:chelerythrine; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; C070515:bisindolylmaleimide I; D000077191:Wortmannin