AMY-1 interacts with S-AKAP84 and AKAP95 in the cytoplasm and the nucleus, respectively, and inhibits cAMP-dependent protein kinase activity by preventing binding of its catalytic subunit to A-kinase-anchoring protein (AKAP) complex.

We have reported that a novel c-Myc-binding protein, AMY-1, binds to cAMP-dependent protein kinase-anchoring protein 149 (AKAP149) and its splicing variant, AKAP84 and is localized in the mitochondria in a complex with RII, a regulatory subunit of cAMP-dependent protein kinase (PKA) (Furusawa, M., Ohnishi, T., Taira, T., Iguchi-Ariga, S. M. ...
M., and Ariga, H. (2001) J. Biol. Chem. 276, 36647-36651). In this study, we further found that AMY-1 competitively bound to either AKAP95 or AKAP84 in the nucleus and the cytoplasm, respectively, in a concentration-dependent manner of either AKAP. Like AKAP84, AMY-1 was found to bind to the RII-binding region of AKAP95 in vivo and in vitro and to make a ternary complex with RII. It was also found that the formation of the complex of AMY-1 with AKAP84/95 and RII prevented a catalytic subunit from binding to this AKAP complex, leading to suppression of PKA activity. These findings suggest that AMY-1 is an important modulator of PKA.
Mesh Terms:
A Kinase Anchor Proteins, Adaptor Proteins, Signal Transducing, Alternative Splicing, Binding Sites, Carrier Proteins, Cell Line, Cell Nucleus, Cyclic AMP-Dependent Protein Kinases, Cytoplasm, DNA-Binding Proteins, Genes, myc, Genetic Variation, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Nuclear Proteins, Plasmids, Protein Subunits, Recombinant Proteins, Transcription Factors, Transfection, Zinc Fingers
J. Biol. Chem.
Date: Dec. 27, 2002
Download Curated Data For This Publication
452
Switch View:
  • Interactions 5