Antibody-induced mitogenicity mediated by a chimeric CD2-c-fms receptor.
A chimeric receptor composed of the extracellular domain of the human T-cell antigen CD2 (T11) joined to the membrane-spanning segment and the intracellular tyrosine kinase domain of the human colony-stimulating factor 1 receptor (CSF-1R) was expressed in murine NIH 3T3 fibroblasts. Stimulation of these cells with monoclonal antibodies to CD2 induced phosphorylation of the chimeric glycoprotein on tyrosine, receptor downmodulation, and mitogenesis. In contrast, neither human CSF-1R nor the chimeric receptor was able to function in interleukin-2-dependent murine T cells. In fibroblasts, then, CSF-1 per se is not required for activation of the receptor kinase or for a biological response, whereas in T cells, CSF-1R may be unable to engage the downstream signal transduction machinery.
Department of Tumor Cell Biology, St. Jude Children's Research Hospitals, Memphis, Tennessee 38105.
M F
MF
Roussel
C
C
Transy
J Y
JY
Kato
E L
EL
Reinherz
C J
CJ
Sherr
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001483:Base Sequence; D018801:CD2 Antigens; D002455:Cell Division; D015536:Down-Regulation; D000939:Epitopes; D008969:Molecular Sequence Data; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D015183:Restriction Mapping; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D000939:Epitopes; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor