Cross Talk Between Phosphatidylinositol 3-kinase and Cyclic AMP (cAMP)-protein Kinase a Signaling Pathways at the Level of a Protein Kinase B/beta-arrestin/cAMP Phosphodiesterase 4 Complex

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2010 Jan 21

PMID 20086095

Citations 31

Authors

Elisa Bjorgo

Silje A Solheim

Hilde Abrahamsen

George S Baillie

Kim M Brown

Torunn Berge

Klaus Okkenhaug

Miles D Houslay

Kjetil Tasken

Affiliations

Soon will be listed here.

Abstract

Engagement of the T-cell receptor (TCR) in human primary T cells activates a cyclic AMP (cAMP)-protein kinase A (PKA)-Csk inhibitory pathway that prevents full T-cell activation in the absence of a coreceptor stimulus. Here, we demonstrate that stimulation of CD28 leads to recruitment to lipid rafts of a beta-arrestin/phosphodiesterase 4 (PDE4) complex that serves to degrade cAMP locally. Redistribution of the complex from the cytosol depends on Lck and phosphatidylinositol 3-kinase (PI3K) activity. Protein kinase B (PKB) interacts directly with beta-arrestin to form part of the supramolecular complex together with sequestered PDE4. Translocation is mediated by the PKB plextrin homology (PH) domain, thus revealing a new role for PKB as an adaptor coupling PI3K and cAMP signaling. Functionally, PI3K activation and phosphatidylinositol-(3,4,5)-triphosphate (PIP3) production, leading to recruitment of the supramolecular PKB/beta-arrestin/PDE4 complex to the membrane via the PKB PH domain, results in degradation of the TCR-induced cAMP pool located in lipid rafts, thereby allowing full T-cell activation to proceed.

Citing Articles

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