Lack of requirement for SHP-1 in both Fas-mediated and perforin-mediated cell death induced by CTL.
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.
Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
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H
Takayama
M H
MH
Lee
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Shirota-Someya
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011817:Rabbits; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D003208:Concanavalin A; D054353:Perforin; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse