AKAP5 explained

A-kinase anchor protein 5 is a protein that in humans is encoded by the AKAP5 gene.^{[1] [2] [3]}

Function

The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene is intronless and encodes a member of the AKAP family. The encoded protein binds to the RII-beta regulatory subunit of PKA, and also to protein kinase C and the phosphatase calcineurin. It is predominantly expressed in cerebral cortex and may anchor the PKA protein at postsynaptic densities (PSD) and be involved in the regulation of postsynaptic events. It is also expressed in T lymphocytes and may function to inhibit interleukin 2 transcription by disrupting calcineurin-dependent dephosphorylation of NFAT.

Interactions

AKAP5 has been shown to interact with:

• Calcineurin^[4] and
• GABRB3.^[5]

Further reading

• Lester LB, Scott JD . Anchoring and scaffold proteins for kinases and phosphatases . Recent Prog. Horm. Res. . 52 . 409–29; discussion 429–30 . 1997 . 9238861 .
• Michel JJ, Scott JD . AKAP mediated signal transduction . Annu. Rev. Pharmacol. Toxicol. . 42 . 235–57 . 2002 . 11807172 . 10.1146/annurev.pharmtox.42.083101.135801 .
• Hirsch AH, Glantz SB, Li Y . Cloning and expression of an intron-less gene for AKAP 75, an anchor protein for the regulatory subunit of cAMP-dependent protein kinase II beta . J. Biol. Chem. . 267 . 4 . 2131–4 . 1992 . 10.1016/S0021-9258(18)45852-8 . 1733921 . etal. free .
• Carr DW, Stofko-Hahn RE, Fraser ID . Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif . J. Biol. Chem. . 266 . 22 . 14188–92 . 1991 . 10.1016/S0021-9258(18)98665-5 . 1860836 . etal. free .
• Coghlan VM, Perrino BA, Howard M . Association of protein kinase A and protein phosphatase 2B with a common anchoring protein . Science . 267 . 5194 . 108–11 . 1995 . 7528941 . 10.1126/science.7528941 . 1995Sci...267..108C . etal.
• Glantz SB, Li Y, Rubin CS . Characterization of distinct tethering and intracellular targeting domains in AKAP75, a protein that links cAMP-dependent protein kinase II beta to the cytoskeleton . J. Biol. Chem. . 268 . 17 . 12796–804 . 1993 . 10.1016/S0021-9258(18)31458-3 . 8509414 . free .
• Faux MC, Scott JD . Regulation of the AKAP79-protein kinase C interaction by Ca2+/Calmodulin . J. Biol. Chem. . 272 . 27 . 17038–44 . 1997 . 9202019 . 10.1074/jbc.272.27.17038 . free .
• Kashishian A, Howard M, Loh C . AKAP79 inhibits calcineurin through a site distinct from the immunophilin-binding region . J. Biol. Chem. . 273 . 42 . 27412–9 . 1998 . 9765270 . 10.1074/jbc.273.42.27412 . etal. free .
• Paolillo M, Feliciello A, Porcellini A . The type and the localization of cAMP-dependent protein kinase regulate transmission of cAMP signals to the nucleus in cortical and cerebellar granule cells . J. Biol. Chem. . 274 . 10 . 6546–52 . 1999 . 10037748 . 10.1074/jbc.274.10.6546 . etal. free .
• Dodge KL, Carr DW, Sanborn BM . Protein kinase A anchoring to the myometrial plasma membrane is required for cyclic adenosine 3',5'-monophosphate regulation of phosphatidylinositide turnover . Endocrinology . 140 . 11 . 5165–70 . 1999 . 10537145 . 10.1210/endo.140.11.7133 . free .
• Fraser ID, Cong M, Kim J . Assembly of an A kinase-anchoring protein-beta(2)-adrenergic receptor complex facilitates receptor phosphorylation and signaling . Curr. Biol. . 10 . 7 . 409–12 . 2000 . 10753752 . 10.1016/S0960-9822(00)00419-X . etal. free .
• Sík A, Gulácsi A, Lai Y . Localization of the A kinase anchoring protein AKAP79 in the human hippocampus . Eur. J. Neurosci. . 12 . 4 . 1155–64 . 2000 . 10762347 . 10.1046/j.1460-9568.2000.00002.x . 40933732 . etal.
• Colledge M, Dean RA, Scott GK . Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex . Neuron . 27 . 1 . 107–19 . 2000 . 10939335 . 10.1016/S0896-6273(00)00013-1 . etal. free .
• Indolfi C, Stabile E, Coppola C . Membrane-bound protein kinase A inhibits smooth muscle cell proliferation in vitro and in vivo by amplifying cAMP-protein kinase A signals . Circ. Res. . 88 . 3 . 319–24 . 2001 . 11179200 . 10.1161/01.res.88.3.319. etal. free .
• Dart C, Leyland ML . Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, Kir2.1 . J. Biol. Chem. . 276 . 23 . 20499–505 . 2001 . 11287423 . 10.1074/jbc.M101425200 . free .
• Xie G, Raufman JP . Association of protein kinase A with AKAP150 facilitates pepsinogen secretion from gastric chief cells . Am. J. Physiol. Gastrointest. Liver Physiol. . 281 . 4 . G1051–8 . 2001 . 10.1152/ajpgi.2001.281.4.G1051 . 11557526 . 20939022 . free .

Notes and References

1. Carr DW, Stofko-Hahn RE, Fraser ID, Cone RD, Scott JD . Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79 . J Biol Chem . 267 . 24 . 16816–23 . Sep 1992 . 10.1016/S0021-9258(18)41856-X . 1512224 . free .
2. Carr DW, Hausken ZE, Fraser ID, Stofko-Hahn RE, Scott JD . Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain . J Biol Chem . 267 . 19 . 13376–82 . Aug 1992 . 10.1016/S0021-9258(18)42221-1 . 1618839 . free .
3. Web site: Entrez Gene: AKAP5 A kinase (PRKA) anchor protein 5.
4. Oct 1998 . Kashishian A, Howard M, Loh C, Gallatin WM, Hoekstra MF, Lai Y . AKAP79 inhibits calcineurin through a site distinct from the immunophilin-binding region . J. Biol. Chem. . 273 . 42 . 27412–9 . 9765270 . 10.1074/jbc.273.42.27412. free .
5. Jan 2003 . Brandon NJ, Jovanovic JN, Colledge M, Kittler JT, Brandon JM, Scott JD, Moss SJ . A-kinase anchoring protein 79/150 facilitates the phosphorylation of GABA(A) receptors by cAMP-dependent protein kinase via selective interaction with receptor beta subunits . Mol. Cell. Neurosci. . 22 . 1 . 87–97 . 12595241 . 10.1016/s1044-7431(02)00017-9. 6172436 .