Table 2.
Danger signaling pathways characterized as traffickers of DAMPs.
| DAMPs | Role of ROS | Role of ER stress | Role of autophagy | Role of chaperone-mediated autophagy | Role of secretory pathway | Caspase activity | Role of lysosomes | Comments | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Secreted ATP | + | +/0 | +/0 | 0 | +/0 | + | +/0 | Underlying pathway is highly inducer dependent | (34, 35, 111–113) |
| Released HMGB1 | 0 | 0 | + | ? | 0 | – | ? | Mostly released passively on account of necrosis; only DT-EGF reported to cause active secretion so far | (73, 114, 115) |
| Secreted or surface HSP70 | ? | ? | ? | ? | ? | + | + | ABC transporters help in endolysosomal-secretion; HSP70 has also been reported to be secreted in an exosome surface-bound format | (116–122) |
| Surface CRT | + | + | −/0 | + | + | +/0 | ? | LRP1/lipid rafts mediate surface tethering; components that positively regulate surface-CRT in an inducer-dependent fashion: ERp57, PI3K p110α, BAX/BAK, cytosolic ER-Ca2+, BAP31; of note, anthracycline-induced pathway of surface CRT induction has been found to be conserved from yeast to mammals | (34, 35, 111, 112, 116, 123, 124) |
| Surface HSP90 | + | + | – | ? | + | + | ? | – | (30, 125) |
“+” denotes ability to positively regulate trafficking; “−” denotes ability to negatively regulate trafficking; “0” denotes confirmation of no role in regulation of trafficking and “?” denotes that the role in regulating the trafficking is unknown; “+/0” denotes positive or no role in regulation of trafficking in an inducer-dependent fashion; “−/0” denotes negative or no role in regulation of trafficking in an inducer-dependent fashion.
ATP, adenosine triphosphate; CRT, calreticulin; DT-EGF, epidermal growth factor receptor-targeted diphtheria toxin; ER, endoplasmic reticulum; HMGB1, high-mobility group box 1 protein; HSP, heat shock protein; LRP1, low-density lipoprotein receptor-related protein 1; ROS, reactive oxygen species.