Selective up-regulation of phosphatidylinositol 3'-kinase activity in Th2 cells inhibits caspase-8 cleavage at the death-inducing complex: a mechanism for Th2 resistance from Fas-mediated apoptosis
| Autor: | A S, Varadhachary, M E, Peter, S N, Perdow, P H, Krammer, P, Salgame |
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| Rok vydání: | 1999 |
| Předmět: |
CD3 Complex
Fas-Associated Death Domain Protein CASP8 and FADD-Like Apoptosis Regulating Protein Apoptosis Lymphocyte Activation Catalysis Phosphatidylinositol 3-Kinases Th2 Cells Humans fas Receptor Enzyme Inhibitors Adaptor Proteins Signal Transducing Phosphoinositide-3 Kinase Inhibitors Caspase 8 Hydrolysis Intracellular Signaling Peptides and Proteins Th1 Cells Caspase Inhibitors Caspase 9 Immunity Innate Peptide Fragments Clone Cells Up-Regulation Androstadienes Enzyme Activation Caspases Carrier Proteins Wortmannin Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 163(9) |
| ISSN: | 0022-1767 |
| Popis: | In this study the mechanism of differential sensitivity of CD3-activated Th1- and Th2-type cells to Fas-mediated apoptosis was explored. We show that the Fas-associated death domain protein (FADD)/caspase-8 pathway is differentially regulated by CD3 activation in the two subsets. The apoptosis resistance of activated Th2-type cells is due to an incomplete processing of caspase-8 at the death-inducing signaling complex (DISC) whereas recruitment of caspase-8 to the DISC of Th1- and Th2-like cells is comparable. Activation of phosphatidylinositol 3'-kinase upon ligation of CD3 in Th2-type cells blocked caspase-8 cleavage to its active fragments at the DISC, thereby preventing induction of apoptosis. This study offers a new pathway for phosphatidylinositol 3'-kinase in mediating protection from Fas-induced apoptosis. |
| Databáze: | OpenAIRE |
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