Title

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

Document Type

Article

Publication Date

11-2003

Journal

Molecular and Cellular Biology

Volume

23

Issue

22

First Page

8042

Last Page

8057

URL with Digital Object Identifier

10.1128/MCB.23.22.8042-8057.2003

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.