TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Aichem, Annette
A1  - Masilamani, Madhan
A1  - Illges, Harald
T1  - Redox regulation of CD21 shedding involves signaling via PKC and indicates the formation of a juxtamembrane stalk
JF  - J Cell Sci (Journal of Cell Science)
N2  - Soluble CD21 (sCD21), released from the plasma membrane by proteolytic cleavage (shedding) of its extracellular domain (ectodomain) blocks B cell/follicular dendritic cell interaction and activates monocytes. We show here that both serine- and metalloproteases are involved in CD21 shedding. Using the oxidant pervanadate to mimic B cell receptor activation and thiol antioxidants such as N-acetylcysteine (NAC) and glutathione (GSH) we show that CD21 shedding is a redox-regulated process inducible by oxidation presumably through activation of a tyrosine kinase-mediated signal pathway involving protein kinase C (PKC), and by reducing agents that either directly activate the metalloprotease and/or modify intramolecular disulfide bridges within CD21 and thereby facilitate access to the cleavage site. Lack of short consensus repeat 16 (SCR16) abolishes CD21 shedding, and opening of the disulfide bridge between cys-2 (Cys941) and cys-4 (Cys968) of SCR16 is a prerequisite for CD21 shedding. Replacing these cysteines with selenocysteines (thereby changing the redox potential from -180 to -381 mV) results in a loss of inducible CD21 shedding, and removing this bridge by exchanging these cysteines with methionines increases CD21 shedding.
KW  - Complement receptor
KW  - Cell activation
KW  - Selenocysteine
KW  - B cells
KW  - Redox potential
KW  - Diselenide bridge
KW  - CD21
SN  - 0021-9533
SS  - 0021-9533
U6  - https://doi.org/10.1242/jcs.02984
DO  - https://doi.org/10.1242/jcs.02984
PM  - 16803874
VL  - 119
IS  - 14
SP  - 2892
EP  - 2902
PB  - The Company of Biologists
ER  -