TY - JOUR
T1 - Phosphatidylinositol 3′-kinase blocks CD95 aggregation and caspase-8 cleavage at the death-inducing signaling complex by modulating lateral diffusion of CD95
AU - Varadhachary, Arun S.
AU - Edidin, Michael
AU - Hanlon, Allison M.
AU - Peter, Marcus E.
AU - Krammer, Peter H.
AU - Salgame, Padmini
PY - 2001/5/1
Y1 - 2001/5/1
N2 - Activation of phosphatidylinositol 3′-kinase (PI 3′-K) after ligation of CD3 protects Th2 cells from CD95-mediated apoptosis. Here we show that protection is achieved by inhibition of the formation of CD95 aggregates and consequent activation of caspase-8. Inhibition of aggregate formation is mediated by changes in the actin cytoskeleton, which in turn inhibit lateral diffusion of CD95, reducing its diffusion coefficient, D, 10-fold. After cytochalasin D treatment of stimulated cells, the lateral diffusion of CD95 increases to the value measured on unstimulated cells, and CD95 molecules aggregate to process caspase-8 and mediate apoptosis. Regulation of functional receptor formation by modulating lateral diffusion is a novel mechanism for controlling receptor activity.
AB - Activation of phosphatidylinositol 3′-kinase (PI 3′-K) after ligation of CD3 protects Th2 cells from CD95-mediated apoptosis. Here we show that protection is achieved by inhibition of the formation of CD95 aggregates and consequent activation of caspase-8. Inhibition of aggregate formation is mediated by changes in the actin cytoskeleton, which in turn inhibit lateral diffusion of CD95, reducing its diffusion coefficient, D, 10-fold. After cytochalasin D treatment of stimulated cells, the lateral diffusion of CD95 increases to the value measured on unstimulated cells, and CD95 molecules aggregate to process caspase-8 and mediate apoptosis. Regulation of functional receptor formation by modulating lateral diffusion is a novel mechanism for controlling receptor activity.
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U2 - 10.4049/jimmunol.166.11.6564
DO - 10.4049/jimmunol.166.11.6564
M3 - Article
C2 - 11359808
AN - SCOPUS:0035336166
SN - 0022-1767
VL - 166
SP - 6564
EP - 6569
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -