Phosphatidylinositol 3'-kinase blocks CD95 aggregation and caspase-8 cleavage at the death-inducing signaling complex by modulating lateral difusion of CD95

摘要

Activation of phosphatidylinositol 3’-kinase (P1 3’-K) after ligation of CD3 protects Th2 cells from CD95-mediated apoptosis. He; we show that protection is achieved by inhibition of the formation of CD9S aggregates and consequent activation of caspase-Inhibition of aggregate formation is mediated by changes in the actin cytoskeleton, which in turn inhibit lateral diffusion of CD9 reducing its diffusion coefficient, D, 10-fold. After cytochalasin D treatment of stimulated cells, the lateral diffusion of CD5 increases to the value measured on unstimulated cells, and CD95 molecules aggregate to process caspase-8 and mediate apoptosi Regulation of functional receptor formation by modulating lateral diffusion is a novel mechanism for controlling recept( activity.