Specific and common activities of the FLT3 and KIT tyrosine kinase receptors revealed by the use of cultured mast cells.
Development of the hematopoietic lineages is partially under the control of hematopoietic receptors with tyrosine kinase activity (RTK). To compare the cellular functions of two of the class III RTK, FLT3 and KIT, a murine chimeric FMS/FLT3 (FF3) receptor was expressed ectopically using retroviral infection, in normal IL3-derived cultured mast cells. Stimulation of the chimeric receptor produced a full mitogenic signal and led to mast cell maturation, as occurs upon activation of the endogenous KIT receptor. When introduced into mast cells derived from KIT-deficient White spotting (W) mutant mice, the FF3 receptor bypassed their mitogenic defect. KIT activation induced a synergistic mitogenic activity in mast cells upon IL3 stimulation, whereas FF3 appeared to down-modulate the IL3 response. Adhesion to fibronectin was specifically associated with KIT signaling.
Molecular and Functional Hematology Laboratory U119 INSERM, Marseille, France.
N
N
Casteran
N
N
Beslu
E
E
Lecocq
S
S
Gomez
P
P
Dubreuil
D000581:Amidohydrolases; D000626:Aminopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000648:ultrastructure; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D008099:Liver / Q000166:cytology; D008297:Male; D008407:Mast Cells / Q000502:physiology / Q000648:ultrastructure*; D051379:Mice; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012680:Sensitivity and Specificity; D051941:fms-Like Tyrosine Kinase 3
D005353:Fibronectins; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D016185:Receptors, Interleukin-3; D011993:Recombinant Fusion Proteins; C497971:Flt3 protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase