Phosphatidylinositol 3′-Kinase blocks CD95 aggregation and caspase-8 cleavage at the death-inducing signaling complex by modulating lateral diffusion of CD95

• Verfasst von: Varadhachary, Arun S. [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Phosphatidylinositol 3′-Kinase blocks CD95 aggregation and caspase-8 cleavage at the death-inducing signaling complex by modulating lateral diffusion of CD95
• Verf.angabe: Arun S. Varadhachary, Michael Edidin, Allison M. Hanlon, Marcus E. Peter, Peter H. Krammer, and Padmini Salgame
• E-Jahr: 2001
• Jahr: June 1, 2001
• Umfang: 6 S.
• Teil: volume:166
• Teil: year:2001
• Teil: number:11
• Teil: pages:6564-6569
• Teil: extent:6
• Fussnoten: Gesehen am 20.04.2021
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2001
• Band/Heft Quelle: 166(2001), 11, Seite 6564-6569
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.166.11.6564
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1755419848

Abstract

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.