Phosphatidylinositol 3′-Kinase blocks CD95 aggregation and caspase-8 cleavage at the death-inducing signaling complex by modulating lateral diffusion of CD95
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 mediat...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 1, 2001
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| In: |
The journal of immunology
Year: 2001, Volume: 166, Issue: 11, Pages: 6564-6569 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.166.11.6564 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.166.11.6564 Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/166/11/6564 
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| Author Notes: | Arun S. Varadhachary, Michael Edidin, Allison M. Hanlon, Marcus E. Peter, Peter H. Krammer, and Padmini Salgame |
| Summary: | 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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| Item Description: | Gesehen am 20.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.166.11.6564 |