Swapping between Fas and granulocyte colony-stimulating factor receptor

Area of Science:

• Cell Biology
• Molecular Biology
• Immunology

Background:

• Fas receptor initiates apoptosis upon Fas ligand binding.
• Granulocyte colony-stimulating factor receptor (G-CSFR) regulates neutrophil development.
• Receptor families typically mediate distinct cellular functions.

Purpose of the Study:

• To investigate functional exchange between the Fas and G-CSFR signaling pathways.
• To construct and express chimeric receptors combining Fas and G-CSFR domains.
• To determine how domain swapping affects receptor-mediated cell signaling.

Main Methods:

• Construction of Fas/G-CSFR hybrid receptors.
• Expression of chimeric receptors in mouse T cell (WR19L) and myeloid (FDC-P1) lines.
• Stimulation of cells with Fas ligand, anti-Fas antibody, G-CSF, and anti-G-CSFR antibody.

Main Results:

• Chimeric receptors with Fas extracellular and G-CSFR cytoplasmic regions induced proliferation upon Fas stimulation.
• Chimeric receptors with G-CSFR extracellular and Fas cytoplasmic regions did not induce apoptosis with G-CSF but were killed by anti-G-CSFR antibody.
• Demonstrated functional interchangeability between different receptor families.

Conclusions:

• Receptors from distinct families can functionally substitute for each other.
• G-CSFR homodimerization transduces growth signals.
• Fas receptor requires oligomerization (likely trimerization) for apoptotic signal transduction.