Di Benedetto, G., Zoccarato, A., Lissandron, V., Terrin, A., Li, X., Houslay, M. D., Baillie, G. S. and Zaccolo, M. (2008) Protein kinase A type I and type II define distinct intracellular signaling compartments. Circulation Research, 103(8), pp. 836-844. (doi: 10.1161/CIRCRESAHA.108.174813)
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Publisher's URL: http://dx.doi.org/10.1161/CIRCRESAHA.108.174813
Abstract
Protein kinase (PK)A is a key regulatory enzyme that, on activation by cAMP, modulates a wide variety of cellular functions. PKA isoforms type I and type II possess different structural features and biochemical characteristics, resulting in nonredundant function. However, how different PKA isoforms expressed in the same cell manage to perform distinct functions on activation by the same soluble intracellular messenger, cAMP, remains to be established. Here, we provide a mechanism for the different function of PKA isoforms subsets in cardiac myocytes and demonstrate that PKA-RI and PKA-RII, by binding to AKAPs (A kinase anchoring proteins), are tethered to different subcellular locales, thus defining distinct intracellular signaling compartments. Within such compartments, PKA-RI and PKA-RII respond to distinct, spatially restricted cAMP signals generated in response to specific G protein-coupled receptor agonists and regulated by unique subsets of the cAMP degrading phosphodiesterases. The selective activation of individual PKA isoforms thus leads to phosphorylation of unique subsets of downstream targets.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Baillie, Professor George and Houslay, Professor Miles and Zaccolo, Professor Manuela and Terrin, Ms Anna |
| Authors: | Di Benedetto, G., Zoccarato, A., Lissandron, V., Terrin, A., Li, X., Houslay, M. D., Baillie, G. S., and Zaccolo, M. |
| Subjects: | Q Science > QH Natural history > QH345 Biochemistry |
| 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: | Circulation Research |
| Publisher: | Lippincott Williams & Wilkins |
| ISSN: | 0009-7330 |
| ISSN (Online): | 1524-4571 |
| Published Online: | 28 August 2008 |
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