Abstract
Fas belongs to the tumor necrosis factor/nerve growth factor receptor family. The Fas ligand binds to its receptor, Fas, and induces apoptosis in Fas-bearing cells. The granulocyte colony-stimulating factor receptor (G-CSFR) is a member of the hemopoietic growth factor receptor family. G-CSF induces its dimerization and regulates the proliferation and differentiation of neutrophilic granulocytes. We constructed hybrid receptors between Fas and G-CSFR and expressed them in the mouse T cell line WR19L or the mouse myeloid interleukin-3-dependent FDC-P1 cell line. The Fas ligand or an agonistic anti-Fas antibody stimulated proliferation of the FDC-P1 transformants expressing a chimera consisting of the Fas extracellular and G-CSFR cytoplasmic regions. On the other hand, G-CSF could not induce apoptosis in the transformants expressing the chimera consisting of the G-CSFR extracellular and Fas cytoplasmic regions, but these cells were killed by a polyclonal antibody against G-CSFR. These results indicated that receptors belonging to different receptor families can be functionally exchanged and confirm that a homodimer of G-CSFR can transduce the growth signal, whereas Fas must be oligomerized (probably trimerized) to transduce the apoptotic signal.
Highlights
Eration and differentiation of neutrophilic progenitor cells
Fas ligand (FasL) or anti-Fas antibody stimulated growth of the transformants (Fig. 3, c and d), and these transformants could be maintained in the presence of FasL or antiFas antibody. These results indicated that FasL or anti-Fas antibody bound to the extracellular region of Fas in the Fas/G chimera and activated the G-colonystimulating factors (CSFs) receptor (G-CSFR) cytoplasmic region to transduce the growth signal
We have shown that binding of polyclonal anti-G-CSFR antibody to granulocyte colony-stimulating factor receptor (GCSFR) activated the G-CSF cytoplasmic region to transduce the growth signal
Summary
The G-CSF receptor (G-CSFR) is a type I membrane protein belonging to the hemopoietic growth factor receptor family [3, 4], which includes the receptors for interleukins (ILs), colonystimulating factors (CSFs), and growth hormone. Called APO-1 or CD95, is a 45-kDa type I membrane protein expressed in various tissues and cells and belongs to the TNF/nerve growth factor (NGF) receptor family (6 –9). This family is comprised of TNF receptors (type I,  or 55 kDa; type II, ␣ or 75 kDa), low affinity NGF receptor, the B cell antigen.
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