A comparison of the cytoplasmic domains of the Fas receptor and the p75 neurotrophin receptor.
The p75 neurotrophic receptor (p75) shares structural features with the Fas receptor (FasR). Both receptors contain extracellular cysteine-rich repeats, a single transmembrane domain, and intracellular death domains. However, it has not been clearly established whether their death domains are equivalent in their ability to mediate apoptosis. To understand better the role of p75 during apoptosis, we constructed chimeric receptors that contained the extracellular portion of the FasR and the intracellular portion of p75. These chimeric receptors, one containing the p75 transmembrane domain and the other containing the FasR transmembrane portion, as well as wild-type p75 and Fas receptors, were transiently transfected into human U373 glioma cells and human embryonic kidney 293 cells (293 cells), which are both responsive to Fas-mediated apoptosis. Whereas expression of FasR was sufficient to induce apoptosis in U373 and 293 cells, expression of p75 and the chimeric receptors induced only minimal levels of cell death compared to FasR. The results indicate that the magnitudes of FasR- and p75-induced killing are different and suggest that the death domain of p75 does not function in the same manner as the FasR death domain.
Kong
H
H
Molecular Neurobiology Program, Skirball Institute, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA.
Kim
A H
AH
Orlinick
J R
JR
Chao
M V
MV
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002461:Cell Line, Transformed; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D020800:Receptor, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D019014:fas Receptor