Sheddase
From Wikipedia, the free encyclopedia
Sheddases are membrane-bound enzymes that cleave extracellular portions of transmembrane proteins, releasing the soluble ectodomains from the cell surface. Many sheddases are members of the ADAM or aspartic protease (BACE) protein families.[1]
These enzymes can activate a transmembrane protein if it is a receptor (e.g., HER2), or cut off the part of the transmembrane protein which has already bound an agonist (e.g., in the case of EGFR), allowing this agonist to go and stimulate a receptor on another cell. Hence, sheddases demultiply[clarification needed] the yield of agonists. Sheddase inhibitors active on ADAM10 and ADAM17 can potentiate anti-cancer therapy.[2]
It has been postulated that the activity of sheddases occurs in relation to the amount of general enzymatic activity. Research indicates that sheddases are instead related to phosphatidylserine exposure. When PSA-3 cells' ability to synthesize phosphatidylserine was repressed, sheddase activity decreased, and the sheddase activity returned to normal levels when the cells were again able to synthesize phosphatidylserine. This led researchers to conclude that phosphatidyserine exposure is necessary for cells to exhibit sheddase activity.[3]
