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AKAP95 Organizes a Nuclear Microdomain to Control Local cAMP for Regulating Nuclear PKA
Terri Clister1, Eric C Greenwald2, George S Baillie3
1Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology, University of California, 9500 Gilman Drive, BRF-II 1120, La Jolla, CA 92093-0702, USA.
Abstract:
Contrary to the classic model of protein kinase A (PKA) residing outside of the nucleus, we identify a nuclear signaling complex that consists of AKAP95, PKA, and PDE4D5 and show that it forms a functional cyclic AMP (cAMP) signaling microdomain. Locally generated cAMP can accumulate within the vicinity of this complex; however, when cAMP is generated at the plasma membrane, PDE4 serves as a local sink and PDE3 as a barrier to prevent accumulation of cAMP within the microdomain as a means of controlling activation of tethered nuclear PKA.
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