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.
Furusawa
Makoto
M
Graduate School of Pharmaceutical Sciences, College of Medical Technology, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
Taira
Takahiro
T
Iguchi-Ariga
Sanae M M
SM
Ariga
Hiroyoshi
H
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016259:Genes, myc; D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids; D021122:Protein Subunits / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D016335:Zinc Fingers
D054758:A Kinase Anchor Proteins; C105137:AKAP1 protein, human; C490117:AKAP8L protein, human; D048868:Adaptor Proteins, Signal Transducing; C486332:Akap1 protein, rat; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C116115:MYCBP protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D011994:Recombinant Proteins; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases