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Lack of requirement for SHP-1 in both Fas-mediated and perforin-mediated cell death induced by CTL
H Takayama1, M H Lee, Y Shirota-Someya
1Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Abstract:
The Fas (CD95)-transmitted cell death signal has been reported to involve a protein tyrosine phosphatase, SHP-1. We analyzed the role of SHP-1 in the Fas-dependent as well as the perforin-dependent pathways of CTL-mediated killing using target cells prepared from SHP-1-deficient motheaten mice. Con A blast targets prepared from both a motheaten mouse and a phenotype-normal littermate were equally sensitive to the cytolysis and DNA fragmentation induced by both perforin-deficient Fas-dependent CTL and Fas ligand-deficient perforin-positive CTL. Fas-induced DNA degradation detected by the terminal deoxynucleotide transferase reaction was also observed in the killing of motheaten thymocytes by a Fas-based CTL as well as by anti-Fas mAb. These data cast doubt on the involvement of SHP-1 in Fas-induced lymphoid cell death.
Insights
This study investigated the role of SHP-1 in cell death signaling. Findings suggest SHP-1 is not involved in Fas-induced lymphoid cell death pathways.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- The Fas (CD95) receptor initiates a cell death signaling cascade.
- Protein tyrosine phosphatase SHP-1 has been implicated in Fas-mediated apoptosis.
Purpose of the Study:
- To elucidate the role of SHP-1 in cytotoxic T lymphocyte (CTL)-mediated killing pathways.
- To determine if SHP-1 is essential for Fas-dependent and perforin-dependent cytolysis.
Main Methods:
- Utilized target cells from SHP-1-deficient motheaten mice.
- Compared cytolysis and DNA fragmentation in response to Fas-dependent and perforin-dependent CTLs.
- Assessed Fas-induced DNA degradation using terminal deoxynucleotide transferase assays.
Main Results:
- SHP-1-deficient and normal target cells showed equal sensitivity to cytolysis and DNA fragmentation.
- Both perforin-deficient Fas-dependent CTLs and Fas ligand-deficient perforin-positive CTLs induced similar effects.
- Fas-induced DNA degradation was observed in motheaten thymocytes treated with Fas-based CTL or anti-Fas mAb.
Conclusions:
- The involvement of SHP-1 in Fas-induced lymphoid cell death is questionable.
- These findings challenge the established role of SHP-1 in Fas-mediated apoptosis.