Bjorgo, E., Solheim, S. A., Abrahamsen, H., Baillie, G. S. , Brown, K. M., Berge, T., Okkenhaug, K., Houslay, M. D. and Tasken, K. (2010) Cross talk between phosphatidylinositol 3-kinase and cyclic AMP (cAMP)-protein kinase A signaling pathways at the level of a protein kinase B/β-Arrestin/cAMP phosphodiesterase 4 complex. Molecular and Cellular Biology, 30(7), pp. 1660-1672. (doi: 10.1128/MCB.00696-09)
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Publisher's URL: http://dx.doi.org/10.1128/MCB.00696-09
Abstract
Engagement of the T cell receptor (TCR) in human primary T cells activates a cAMP-protein kinase A (PKA)-Csk inhibitory pathway that prohibits full T cell activation in the absence of a co-receptor stimulus. Here, we demonstrate that stimulation of CD28 leads to recruitment of a {beta}-arrestin/phosphodiesterase-4 (PDE4) complex to lipid rafts that serves to degrade cAMP locally. Redistribution of the complex from the cytosol depends on Lck and PI3-kinase (PI3K) activity. Protein kinase B (PKB) interacts directly with β-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 PIP3 production leading to recruitment of the supramolecular PKB/β-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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Houslay, Professor Miles and Baillie, Professor George and Okkenhaug, Dr Klaus |
| Authors: | Bjorgo, E., Solheim, S. A., Abrahamsen, H., Baillie, G. S., Brown, K. M., Berge, T., Okkenhaug, K., Houslay, M. D., and Tasken, K. |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | Molecular and Cellular Biology |
| Publisher: | American Society for Microbiology |
| ISSN: | 0270-7306 |
| ISSN (Online): | 1098-5549 |
| Published Online: | 19 January 2010 |
| Related URLs: |
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