Coordinate expression of the alpha and beta chains of human granulocyte-macrophage colony-stimulating factor receptor confers ligand-induced morphological transformation in mouse fibroblasts.
Two distinct components, alpha and beta chains, which compose the high affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) do not contain any catalytic domains of known enzymes. However, in mouse lymphoid cell lines transfected with cDNAs of the both chains, GM-CSF triggers tyrosine phosphorylation of several cellular proteins and allows continuous proliferation. To elucidate whether the high affinity receptor functions in nonhematopoietic cells, we have reconstituted human GM-CSF receptor in mouse NIH3T3 fibroblasts. In NIH3T3 clones, in which the high affinity receptor is reconstituted, human GM-CSF has triggered rapid tyrosine phosphorylation of cellular proteins, transfected beta chain, and another protein of 40-45 kDa. Moreover, human GM-CSF stimulated DNA synthesis and induced morphological transformation. These observations indicate that coordinately expressed alpha and beta chains of human GM-CSF receptor activates intrinsic protein-tyrosine kinases by the stimulation with human GM-CSF and that the activated protein-tyrosine kinases phosphorylate tyrosine residues of an intrinsic 40-45-kDa protein and the transfected beta chain in NIH3T3 cells. Activation of the protein-tyrosine kinases is likely to have biological functions to induce DNA synthesis and morphological transformation of mouse fibroblasts.
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
K
K
Sasaki
S
S
Chiba
Y
Y
Hanazono
H
H
Mano
Y
Y
Yazaki
H
H
Hirai
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D010766:Phosphorylation; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D008024:Ligands; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D014443:Tyrosine; D004247:DNA