Death receptors bind SHP-1 and block cytokine-induced anti-apoptotic signaling in neutrophils
Author: ["Isabelle Daigle","Shida Yousefi","Marco Colonna","Douglas R. Green","Hans-Uwe Simon"]
Publication: Nature Medicine
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Abstract
Death domain–containing receptors of the tumor necrosis factor (TNF)/nerve growth factor (NGF) family can induce apoptosis upon activation in many cellular systems. We show here that a conserved phosphotyrosine-containing motif within the death domain of these receptors can mediate inhibitory functions. The Src homology domain 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1), SHP-2 and SH2-containing inositol phosphatase (SHIP) bound to this motif in a caspase-independent but cell-dependent manner. We also found that stimulation of death receptors disrupted anti-apoptosis pathways initiated (at least under certain conditions) by survival factors in neutrophils. In these cells, activation of the tyrosine kinase Lyn, an important anti-apoptotic event, was prevented as a consequence of death-receptor stimulation, most likely through association of the receptor with activated SHP-1. Thus, we provide molecular and functional evidence for negative signaling by death receptors.
Cite this article
Daigle, I., Yousefi, S., Colonna, M. et al. Death receptors bind SHP-1 and block cytokine-induced anti-apoptotic signaling in neutrophils. Nat Med 8, 61–67 (2002). https://doi.org/10.1038/nm0102-61
