Death Receptor Signalling

Stable Identifier
R-HSA-73887
Type
Pathway
Species
Homo sapiens
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Summation

The death receptors (DR), all cell-surface receptors, that belong to the TNF receptor superfamily (TNFRSF). The term death receptor refers to those members of the TNFRSF that contain a "death domain" (DD) within their cytoplasmic tail which provides the capacity for protein?protein interactions with other DD-containing proteins suach as FADD. The main signals transmitted from TNF death receptors such as TNFR1, TRAIL-R, and CD95/FAS in response to their cognate ligand binding result in an apoptotic signaling pathway characterized by direct activation of intracellular cysteine proteases (caspases), without directly involving the mitochondrial death pathway. However, these death receptors have also been shown to initiate survival signals via the activation of transcription factors NF?appaB and AP1. This project describes an assembly of the death-inducing signaling complex (DISC) downstream of TNFR1, TRAIL-R, and CD95/FAS and shows protein composition and stoichiometry within the DISC. However, the DISC signaling complex may vary in its components stoichiometry. DR signaling may trigger formation of higher order receptor structures or signaling through rearrangement of receptor chains, which is not reflected here. The project also describes neuron-type-specific signaling by the p75NTR death receptor (also known as NGFR) that can regulate a number of different biological activities in response to ligand binding, including cell death and/or survival, axonal growth and synaptic plasticity.

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