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

Cell Chem Biol. 2019 Jun 20;26(6):885-891.e4. doi: 10.1016/j.chembiol.2019.03.003. Epub 2019 Apr 11.


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.

Keywords: FRET biosensors; compartmentalization; imaging; spatiotemporal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • A Kinase Anchor Proteins / metabolism*
  • Cell Nucleus / enzymology*
  • Cell Nucleus / metabolism*
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • HEK293 Cells
  • Humans
  • Signal Transduction


  • A Kinase Anchor Proteins
  • AKAP8 protein, human
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases