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Gene Review

AKAP1  -  A kinase (PRKA) anchor protein 1

Homo sapiens

Synonyms: A-kinase anchor protein 1, mitochondrial, A-kinase anchor protein 149 kDa, AKAP, AKAP 149, AKAP121, ...
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Disease relevance of AKAP1

  • Gravin staining is coincident with an AKAP detected by an in situ RII-overlay assay, and a PKA-gravin complex can be isolated from human erythroleukemia cells [1].
  • RESULTS: We have identified and characterized another mammalian scaffold protein which coordinates the location of protein kinase A and protein kinase C. We isolated a cDNA encoding a 250 kDa A-skinase anchoring protein (AKAP) called gravin, which was originally identified as a cytoplasmic antigen recognized by myasthenia gravis sera [1].
  • PKA/AKAP/VR-1 module: A common link of Gs-mediated signaling to thermal hyperalgesia [2].

High impact information on AKAP1

  • These methods use FRET probes based upon either protein kinase A (PKA) or EPAC, cAMP-gated ion channels, or the selective activation of AKAP-anchored PKA isoforms [3].
  • AKAP mediated signal transduction [4].
  • Thus, the PKA-mediated regulation of L-type Ca2+ channels is critically dependent on a functional AKAP and phosphorylation of the alpha1C subunit at Ser1928 [5].
  • Furthermore, we have demonstrated that the association of an AKAP with PKA was required for beta-adrenergic receptor-mediated regulation of L-type channels in native cardiac myocytes, illustrating that the events observed in the heterologous expression system reflect those occurring in the native system [5].
  • The PKA, PKC, and protein phosphatase-2B/calcineurin (CaN) scaffold protein A-kinase anchoring protein (AKAP) 79 is localized to excitatory neuronal synapses where it is recruited to glutamate receptors by interactions with membrane-associated guanylate kinase (MAGUK) scaffold proteins [6].

Biological context of AKAP1

  • 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 [7].
  • AMY-1 was also found to be associated with protein kinase A anchor protein 84/149 (S-AKAP84/AKAP149) in the mitochondria in somatic cells and sperm, suggesting that it plays a role in spermatogenesis [8].
  • The 3.2-kilobase S-AKAP84 mRNA and the cognate S-AKAP84 RII binding protein are expressed principally in the male germ cell lineage [9].
  • We propose that kinase and phosphatase anchoring at the NE by AKAP149 plays in a role in modulating nuclear reassembly at the end of mitosis [10].
  • In vivo dissociation of PP1 from NE-bound AKAP149 in G1-phase nuclei triggers phosphorylation and depolymerization of A- and B-type lamins [11].

Anatomical context of AKAP1


Associations of AKAP1 with chemical compounds

  • Dual specificity AKAP1, (D-AKAP1) binds to both type I and type II regulatory subunits and has two NH2-terminal (N0 and N1) and two COOH-terminal (C1 and C2) splice variants (. J. Biol. Chem. 272:8057) [13].
  • Selective siRNA-mediated knockdown identifies AKAP79, which is constitutively associated with the beta2-AR, rather than isoprenaline-recruited gravin, as being the functionally relevant AKAP in this process [14].
  • Thus, AKAP 121/149 contains a KH region that is essential to the translation inhibition of LPL in response to epinephrine [15].
  • PI 3-kinase inhibition results in an increase in intracellular cAMP levels and in tyrosine phosphorylation of the protein kinase A-anchoring protein AKAP3 [16].
  • Peptides with S151 or S159 as the only wt serine residue trigger dissociation of PP1 from immunoprecipitated AKAP149, whereas S151/159D mutants are ineffective [17].

Physical interactions of AKAP1

  • Competition with a peptide covering the RII-binding domain of AKAP Ht31 abolished RIIalpha binding to AKAP95 [18].
  • Purified AKAP121 KH domain binds the 3' untranslated regions (3'UTRs) of transcripts encoding the Fo-f subunit of mitochondrial ATP synthase and manganese superoxide dismutase (MnSOD) [19].

Other interactions of AKAP1


Analytical, diagnostic and therapeutic context of AKAP1

  • Western blot analyses identified four known AKAPs: AKAP79, AKAP95, AKAP149, and WAVE [23].
  • We have now purified the 78 kDa AKAP to homogeneity from gastric fundic mucosal supernates using type II A-kinase regulatory subunit (RII) affinity chromatography [24].
  • Using a combination of protein kinase A type II overlay screening, rapid amplification of cDNA ends, and database searches, a contig of 9923 bp was assembled and characterized in which the open reading frame encoded a 1901-amino-acid A-kinase-anchoring protein (AKAP) with an apparent SDS-PAGE mobility of 220 kDa, named human AKAP220 (hAKAP220) [25].
  • Immunoblotting analysis and trypsin digestion pattern show that 90% or more of mitochondrial C-PKA, R-PKA and AKAP121 is localized in the inner mitochondrial compartment, when prepared both from isolated mitochondria or cardiomyocyte cultures [26].
  • This localization is verified by measurement of the specific catalytic activity of PKA, radiolabelling of R-PKA by (32)P-phosphorylated C-PKA and of AKAP by (32)P-phosphorylated R-PKA and electron microscopy of mitochondria exposed to gold-conjugated AKAP121 antibody [26].


  1. Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein. Nauert, J.B., Klauck, T.M., Langeberg, L.K., Scott, J.D. Curr. Biol. (1997) [Pubmed]
  2. PKA/AKAP/VR-1 module: A common link of Gs-mediated signaling to thermal hyperalgesia. Rathee, P.K., Distler, C., Obreja, O., Neuhuber, W., Wang, G.K., Wang, S.Y., Nau, C., Kress, M. J. Neurosci. (2002) [Pubmed]
  3. Arrestin times for compartmentalised cAMP signalling and phosphodiesterase-4 enzymes. Baillie, G.S., Houslay, M.D. Curr. Opin. Cell Biol. (2005) [Pubmed]
  4. AKAP mediated signal transduction. Michel, J.J., Scott, J.D. Annu. Rev. Pharmacol. Toxicol. (2002) [Pubmed]
  5. cAMP-dependent regulation of cardiac L-type Ca2+ channels requires membrane targeting of PKA and phosphorylation of channel subunits. Gao, T., Yatani, A., Dell'Acqua, M.L., Sako, H., Green, S.A., Dascal, N., Scott, J.D., Hosey, M.M. Neuron (1997) [Pubmed]
  6. Imaging kinase--AKAP79--phosphatase scaffold complexes at the plasma membrane in living cells using FRET microscopy. Oliveria, S.F., Gomez, L.L., Dell'Acqua, M.L. J. Cell Biol. (2003) [Pubmed]
  7. 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. Furusawa, M., Taira, T., Iguchi-Ariga, S.M., Ariga, H. J. Biol. Chem. (2002) [Pubmed]
  8. AAT-1, a novel testis-specific AMY-1-binding protein, forms a quaternary complex with AMY-1, A-kinase anchor protein 84, and a regulatory subunit of cAMP-dependent protein kinase and is phosphorylated by its kinase. Yukitake, H., Furusawa, M., Taira, T., Iguchi-Ariga, S.M., Ariga, H. J. Biol. Chem. (2002) [Pubmed]
  9. Characterization of S-AKAP84, a novel developmentally regulated A kinase anchor protein of male germ cells. Lin, R.Y., Moss, S.B., Rubin, C.S. J. Biol. Chem. (1995) [Pubmed]
  10. Recruitment of protein phosphatase 1 to the nuclear envelope by A-kinase anchoring protein AKAP149 is a prerequisite for nuclear lamina assembly. Steen, R.L., Martins, S.B., Taskén, K., Collas, P. J. Cell Biol. (2000) [Pubmed]
  11. AKAP149 is a novel PP1 specifier required to maintain nuclear envelope integrity in G1 phase. Steen, R.L., Beullens, M., Landsverk, H.B., Bollen, M., Collas, P. J. Cell. Sci. (2003) [Pubmed]
  12. AMY-1, a c-Myc-binding protein, is localized in the mitochondria of sperm by association with S-AKAP84, an anchor protein of cAMP-dependent protein kinase. Furusawa, M., Ohnishi, T., Taira, T., Iguchi-Ariga, S.M., Ariga, H. J. Biol. Chem. (2001) [Pubmed]
  13. NH2-Terminal targeting motifs direct dual specificity A-kinase-anchoring protein 1 (D-AKAP1) to either mitochondria or endoplasmic reticulum. Huang, L.J., Wang, L., Ma, Y., Durick, K., Perkins, G., Deerinck, T.J., Ellisman, M.H., Taylor, S.S. J. Cell Biol. (1999) [Pubmed]
  14. RNA silencing identifies PDE4D5 as the functionally relevant cAMP phosphodiesterase interacting with beta arrestin to control the protein kinase A/AKAP79-mediated switching of the beta2-adrenergic receptor to activation of ERK in HEK293B2 cells. Lynch, M.J., Baillie, G.S., Mohamed, A., Li, X., Maisonneuve, C., Klussmann, E., van Heeke, G., Houslay, M.D. J. Biol. Chem. (2005) [Pubmed]
  15. Role of A kinase anchor proteins in the tissue-specific regulation of lipoprotein lipase. Ranganathan, G., Pokrovskaya, I., Ranganathan, S., Kern, P.A. Mol. Endocrinol. (2005) [Pubmed]
  16. Increased phosphorylation of AKAP by inhibition of phosphatidylinositol 3-kinase enhances human sperm motility through tail recruitment of protein kinase A. Luconi, M., Carloni, V., Marra, F., Ferruzzi, P., Forti, G., Baldi, E. J. Cell. Sci. (2004) [Pubmed]
  17. Association of PP1 with Its Regulatory Subunit AKAP149 Is Regulated by Serine Phosphorylation Flanking the RVXF Motif of AKAP149. Küntziger, T., Rogne, M., Folstad, R.L., Collas, P. Biochemistry (2006) [Pubmed]
  18. Molecular cloning, chromosomal localization, and cell cycle-dependent subcellular distribution of the A-kinase anchoring protein, AKAP95. Eide, T., Coghlan, V., Orstavik, S., Holsve, C., Solberg, R., Skâlhegg, B.S., Lamb, N.J., Langeberg, L., Fernandez, A., Scott, J.D., Jahnsen, T., Taskén, K. Exp. Cell Res. (1998) [Pubmed]
  19. PKA-dependent binding of mRNA to the mitochondrial AKAP121 protein. Ginsberg, M.D., Feliciello, A., Jones, J.K., Avvedimento, E.V., Gottesman, M.E. J. Mol. Biol. (2003) [Pubmed]
  20. Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding. Herberg, F.W., Maleszka, A., Eide, T., Vossebein, L., Tasken, K. J. Mol. Biol. (2000) [Pubmed]
  21. Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2). Li, H., Adamik, R., Pacheco-Rodriguez, G., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  22. A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell lines. Asirvatham, A.L., Galligan, S.G., Schillace, R.V., Davey, M.P., Vasta, V., Beavo, J.A., Carr, D.W. J. Immunol. (2004) [Pubmed]
  23. Identification and characterization of myeloid translocation gene 16b as a novel a kinase anchoring protein in T lymphocytes. Schillace, R.V., Andrews, S.F., Liberty, G.A., Davey, M.P., Carr, D.W. J. Immunol. (2002) [Pubmed]
  24. Ezrin is a cyclic AMP-dependent protein kinase anchoring protein. Dransfield, D.T., Bradford, A.J., Smith, J., Martin, M., Roy, C., Mangeat, P.H., Goldenring, J.R. EMBO J. (1997) [Pubmed]
  25. Localization of a novel human A-kinase-anchoring protein, hAKAP220, during spermatogenesis. Reinton, N., Collas, P., Haugen, T.B., Skâlhegg, B.S., Hansson, V., Jahnsen, T., Taskén, K. Dev. Biol. (2000) [Pubmed]
  26. Occurrence of A-kinase anchor protein and associated cAMP-dependent protein kinase in the inner compartment of mammalian mitochondria. Sardanelli, A.M., Signorile, A., Nuzzi, R., Rasmo, D.D., Technikova-Dobrova, Z., Drahota, Z., Occhiello, A., Pica, A., Papa, S. FEBS Lett. (2006) [Pubmed]
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