Similarity | Difference | ||
---|---|---|---|
TREM-1 | TREM-2 | ||
Structure | Composed of three parts: the extracellular immunoglobulin-like domain, the transmembrane domain and the cytoplasmic domain Two subtypes exist: the membrane-bound type and the soluble type [3,4,5] | Enzyme: MMPs | Enzyme: ADAM 10 and ADAM 17 [5] |
Ligands | HMGB1, HSP70, CD177, actin, PGLYRP1, eCIRP(see “ligands” section) | Cellular debris, lipids, Aβ, nucleic acids, ApoE, LDL [5, 7,8,9] | |
Signaling Pathways | The transmembrane domain undergoes signaling by binding to DAP12 containing the ITAM. ITAM is phosphorylated by Src-family kinase, and recruits Syk to trigger downstream signaling cascades, including PI3K/Akt and MEK/ERK [3,4,5] | Promote inflammation: JAK-STAT3/5, MEK/ERK, PI3K/Akt, NF-κB [6, 128]; Inhibit apoptosis: PI3K/Akt [6]; Promote pyroptosis: NLRP3/caspase-1 [84, 85, 100]; Induce oxidative stress: ROS [84, 127]; Interact with the TLR4 pathway to enhance inflammation [28, 94] | Except DAP12, TREM-2 can also bind to DAP10 [5]; Promote phagocytosis and actin cytoskeleton rearrangement: VAV2/3-Rac1/Cdc42-Arp2/3 [7]; Promote cell growth: Pyk2/β-catenin [7]; Inhibit inflammation: Inhibit NF-κB and MEK/ERK [7, 10]; Inhibit Autophagy: PI3K/Akt-mTOR [11]; |