Distinct signal transduction through the tyrosine-containing domains of the granulocyte colony-stimulating factor receptor.
The receptor for granulocyte colony-stimulating factor (G-CSFR) is a hemopoietic growth factor receptor, which mediates proliferation and differentiation signals. The cytoplasmic region of G-CSFR carries four tyrosine residues in its C-terminal half. We constructed mutant receptors in which each tyrosine residue of G-CSFR was mutated to phenylalanine. Two mutant receptors (Tyr703 and Tyr728) neither transduced the growth-inhibitory signal nor induced the neutrophil-specific myeloperoxidase (MPO) gene. The Tyr703 mutant did not induce morphological changes in cells, whereas transformants expressing the Tyr728 mutant adhered to plates with a macrophage-like morphology upon G-CSF stimulation. Mutation of the most distal tyrosine residue (Tyr763) abolished the ability of G-CSFR to stimulate the tyrosine phosphorylation of a cellular protein with an M(r) of 54 kDa. These results indicated that the regions around the three tyrosine residues of G-CSFR play essential and distinct roles in signal transduction.
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D017353:Gene Deletion; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D009195:Peroxidase / Q000096:biosynthesis; D017354:Point Mutation; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D014443:Tyrosine; D009195:Peroxidase