Regulation of T-Cell Activation by Phosphodiesterase 4B2 Requires Its Dynamic Redistribution during Immunological Synapse Formation-Reference-Cited by-同舟云学术

Regulation of T-Cell Activation by Phosphodiesterase 4B2 Requires Its Dynamic Redistribution during Immunological Synapse Formation

Published:2003-11-15 Issue:22 Volume:23 Page:8042-8057
ISSN:0270-7306
Container-title:Molecular and Cellular Biology
language:en
Short-container-title:Mol Cell Biol

Author:

Arp Jacqueline¹²,Kirchhof Mark G.¹²,Baroja Miren L.¹²,Nazarian Steven H.¹²,Chau Thu A.¹²,Strathdee Craig A.¹,Ball Eric H.³,Madrenas Joaquín¹²

Affiliation:

1. Robarts Research Institute

2. Department of Microbiology and Immunology and Department of Medicine

3. Department of Biochemistry, The University of Western Ontario, London, Ontario, Canada N6A 5K8

Abstract

ABSTRACT Stimulation of T cells through their antigen receptors (TCRs) causes a transient increase in the intracellular concentration of cyclic AMP (cAMP). However, sustained high levels of cAMP inhibit T-cell responses, suggesting that TCR signaling is coordinated with the activation of cyclic nucleotide phosphodiesterases (PDEs). The molecular basis of such a pathway is unknown. Here we show that TCR-dependent signaling activates PDE4B2 and that this enhances interleukin-2 production. Such an effect requires the regulatory N terminus of PDE4B2 and correlates with partitioning within lipid rafts, early targeting of this PDE to the immunological synapse, and subsequent accumulation in the antipodal pole of the T cell as activation proceeds.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Link

https://journals.asm.org/doi/pdf/10.1128/MCB.23.22.8042-8057.2003

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