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AKAP95 Organizes a Nuclear Microdomain to Control Local cAMP for Regulating Nuclear PKA.

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.

SUBMITTER: Clister T

PROVIDER: S-EPMC6588460 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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AKAP95 Organizes a Nuclear Microdomain to Control Local cAMP for Regulating Nuclear PKA.

Clister Terri T Greenwald Eric C EC Baillie George S GS Zhang Jin J

Cell chemical biology 20190411 6

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 con ...[more]

PMID: 30982750

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