A-kinase anchor protein


Function

A-kinase anchor proteins (AKAP) mediate the localization of the cAMP-dependent protein kinase (PKA) and other signaling enzymes by interacting with them [1].

AKAPs form multi-protein complexes via interaction with the regulatory subunits of PKA. These protein complexes are key molecules in the biochemical machinery regulating the function of flagella and cilia[2]. A-kinase anchor protein 10 is also named dual specificity A-kinase anchor protein 2.

  • Small membrane A-kinase anchor protein (smAKAP) is localised at the plasma membrane[3].

Relevance

AKAPs play a central role in organizing signaling pathways which control cardiac contractility and rhythm as well as the pathological response of the heart to stress and other dysfunctions such as arrhythmias, cardiac hypertrophy and heart failure[4].

Structural highlights

An [5]. Hydrophobic, Polar

3D Structures of A-kinase anchor protein

A-kinase anchor protein 3D structures


Human AKAP18 helix (deepskyblue) complex with a dimer of cAMP-dependent protein kinase regulatory subunit (magenta and green) and Cd+2 ions (PDB code 4zp3)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. Edwards AS, Scott JD. A-kinase anchoring proteins: protein kinase A and beyond. Curr Opin Cell Biol. 2000 Apr;12(2):217-21. PMID:10712918
  2. Carr DW, Newell AE. The role of A-kinase anchoring proteins (AKaps) in regulating sperm function. Soc Reprod Fertil Suppl. 2007;63:135-41. PMID:17566268
  3. Burgers PP, Ma Y, Margarucci L, Mackey M, van der Heyden MA, Ellisman M, Scholten A, Taylor SS, Heck AJ. A small novel A-kinase anchoring protein (AKAP) that localizes specifically protein kinase A-regulatory subunit I (PKA-RI) to the plasma membrane. J Biol Chem. 2012 Dec 21;287(52):43789-97. doi: 10.1074/jbc.M112.395970. Epub, 2012 Oct 31. PMID:23115245 doi:http://dx.doi.org/10.1074/jbc.M112.395970
  4. Diviani D, Dodge-Kafka KL, Li J, Kapiloff MS. A-kinase anchoring proteins: scaffolding proteins in the heart. Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1742-53. doi:, 10.1152/ajpheart.00569.2011. Epub 2011 Aug 19. PMID:21856912 doi:http://dx.doi.org/10.1152/ajpheart.00569.2011
  5. Gotz F, Roske Y, Schulz MS, Autenrieth K, Bertinetti D, Faelber K, Zuhlke K, Kreuchwig A, Kennedy E, Krause G, Daumke O, Herberg FW, Heinemann U, Klussmann E. AKAP18:PKA-RIIalpha structure reveals crucial anchor points for recognition of regulatory subunits of PKA. Biochem J. 2016 Apr 21. pii: BCJ20160242. PMID:27102985 doi:http://dx.doi.org/10.1042/BCJ20160242

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