Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

A-Kinase Anchoring Protein (AKAP)

  • Laura Gabrovsek
  • Paula Bucko
  • Graeme K. Carnegie
  • John D. Scott
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_218

Synonyms

Historical Background

Classical physiological experiments identified cAMP as a diffusible intracellular secondary messenger capable of activating cAMP-dependent protein kinase (PKA). These studies defined hormone- and location-specific patterns of PKA activation, suggesting that PKA signaling was compartmentalized. For example, in perfused rat cardiomyocytes, adrenergic stimulation selectively activates a pool of PKA isolated from certain fractions, while prostanoids predominately activate cytosolic PKA (Scott et al. 2013).

The first AKAP to be identified, microtubule-associated protein 2 (MAP2), was copurified with the PKA regulatory subunit subtype II (RII) from rat brain extracts. Over 50 additional AKAP family members have subsequently been identified (Fraser and Scott 1999; Scott et al. 2013). AKAPs are structurally diverse and share little primary sequence similarity, but are functionally similar and are classified by their ability...

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Notes

Acknowledgments

This work was supported by the following grants from the National Institutes of Health: 5R01DK105542 (J.D.S.) and 4P01DK05441 (J.D.S.).

References

  1. Brandon NJ, Jovanovic JN, Colledge M, Kittler JT, Brandon JM, Scott JD, et al. 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. 2003;22:87–97.PubMedCrossRefGoogle Scholar
  2. Canton DA, Keene CD, Swinney K, Langeberg LK, Nguyen V, Pelletier L, et al. Gravin is a transitory effector of polo-like kinase 1 during cell division. Mol Cell. 2012.  https://doi.org/10.1016/j.molcel.2012.09.002.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Carnegie GK, Soughayer J, Smith FD, Pedroja BS, Zhang F, Diviani D, et al. AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway. Mol Cell. 2008;32:169–79.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Chen L, Marquardt ML, Tester DJ, Sampson KJ, Ackerman MJ, Kass RS. Mutation of an A-kinase-anchoring protein causes long-QT syndrome. Proc Natl Acad Sci U S A. 2007;104:20990–5.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Diviani D, Abuin L, Cotecchia S, Pansier L. Anchoring of both PKA and 14-3-3 inhibits the Rho-GEF activity of the AKAP-Lbc signaling complex. EMBO J. 2004;23:2811–20.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Fraser ID, Scott JD. Modulation of ion channels: a “current” view of AKAPs. Neuron. 1999;23:423–6.PubMedCrossRefGoogle Scholar
  7. Gelman IH. Suppression of tumor and metastasis progression through the scaffolding functions of SSeCKS/Gravin/AKAP12. Cancer Metastasis Rev. 2012;31:493–500.  https://doi.org/10.1007/s10555-012-9360-1.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Gold MG, Reichow SL, O’Neill SE, Weisbrod CR, Langeberg LK, Bruce JE, et al. AKAP2 anchors PKA with aquaporin-0 to support ocular lens transparency. EMBO Mol Med. 2012;4:15–26.  https://doi.org/10.1002/emmm.201100184.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Hehnly H, Canton D, Bucko P, Langeberg LK, Ogier L, Gelman I, et al. A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells. eLife. 2015;4:e09384.  https://doi.org/10.7554/eLife.09384.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Hinke SA, Navedo MF, Ulman A, Whiting JL, Nygren PJ, Tian G, et al. Anchored phosphatases modulate glucose homeostasis. EMBO J. 2012;31:3991–4004.  https://doi.org/10.1038/emboj.2012.244.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Hoshi N, Langeberg LK, Gould CM, Newton AC, Scott JD. Interaction with AKAP79 modifies the cellular pharmacology of PKC. Mol Cell. 2010;37:541–50.  https://doi.org/10.1016/j.molcel.2010.01.014.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Huang LJ, Durick K, Weiner JA, Chun J, Taylor SS. Identification of a novel protein kinase A anchoring protein that binds both type I and type II reulatory subunits. J Biol Chem. 1997;272:8057–64.PubMedCrossRefGoogle Scholar
  13. Langeberg LK, Scott JD. Signalling scaffolds and local organization of cellular behaviour. Nat Rev Mol Cell Biol. 2015;16:232–44.  https://doi.org/10.1038/nrm3966.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Lehnart SE, Marks AR. Phosphodiesterase 4D and heart failure: a cautionary tale. Expert Opin Ther Targets. 2006;10:677–88.  https://doi.org/10.1517/14728222.10.5.677.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Li Y, Chen L, Kass RS, Dessauer CW. The A-kinase anchoring protein Yotiao facilitates complex formation between adenylyl cyclase type 9 and the IKs potassium channel in heart. J Biol Chem. 2012;287:29815–24.  https://doi.org/10.1074/jbc.M112.380568.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Means CK, Lygren B, Langeberg LK, Jain A, Dixon RE, Vega AL, et al. An entirely specific type I A-kinase anchoring protein that can sequester two molecules of protein kinase A at mitochondria. Proc Natl Acad Sci USA. 2011;108:E1227–35.  https://doi.org/10.1073/pnas.1107182108.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Mosenden R, Tasken K. Cyclic AMP-mediated immune regulation--overview of mechanisms of action in T cells. Cell Signal. 2011;23:1009–16.  https://doi.org/10.1016/j.cellsig.2010.11.018.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Nauert JB, Klauck TM, Langeberg LK, Scott JD. Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein. Curr Biol. 1997;7:52–62.PubMedCrossRefGoogle Scholar
  19. Navedo MF, Cheng EP, Yuan C, Votaw S, Molkentin JD, Scott JD, et al. Increased coupled gating of L-type Ca2+ channels during hypertension and Timothy syndrome. Circ Res. 2010;106:748–56.  https://doi.org/10.1161/CIRCRESAHA.109.213363.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Newhall KJ, Criniti AR, Cheah CS, Smith KC, Kafer KE, Burkart AD, et al. Dynamic anchoring of PKA is essential during oocyte maturation. Curr Biol. 2006;16:321–7.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Scott JD, Dessauer CW, Tasken K. Creating order from chaos: cellular regulation by kinase anchoring. Annu Rev Pharmacol Toxicol. 2013;53:187–210.  https://doi.org/10.1146/annurev-pharmtox-011112-140204.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Smith FD, Langeberg LK, Cellurale C, Pawson T, Morrison DK, Davis RJ, et al. AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade. Nat Cell Biol. 2010;12:1242–9.  https://doi.org/10.1038/ncb2130.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Smith FD, Reichow SL, Esseltine JL, Shi D, Langeberg LK, Scott JD, et al. Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation. eLife. 2013;2:e01319.  https://doi.org/10.7554/eLife.01319.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Snyder EM, Colledge M, Crozier RA, Chen WS, Scott JD, Bear MF. Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking and long term synaptic depression. J Biol Chem. 2005;280:16962–8.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Soderling SH, Langeberg LK, Soderling JA, Davee SM, Simerly R, Raber J, et al. Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice. Proc Natl Acad Sci USA. 2003;100:1723–8.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Tunquist BJ, Hoshi N, Guire ES, Zhang F, Mullendorff K, Langeberg LK, et al. Loss of AKAP150 perturbs distinct neuronal processes in mice. Proc Natl Acad Sci USA. 2008;105:12557–62.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Whiting JL, Ogier L, Forbush KA, Bucko P, Gopalan J, Seternes OM, et al. AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption. Proc Natl Acad Sci USA. 2016;113:E4328–37.  https://doi.org/10.1073/pnas.1607745113.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Wong W, Scott JD. AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol. 2004;5:959–71.PubMedCrossRefGoogle Scholar
  29. Zhang J, Carver CM, Choveau FS, Shapiro MS. Clustering and functional coupling of diverse ion channels and signaling proteins revealed by super-resolution STORM microscopy in neurons. Neuron. 2016;92:461–78.  https://doi.org/10.1016/j.neuron.2016.09.014.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Laura Gabrovsek
    • 1
  • Paula Bucko
    • 1
  • Graeme K. Carnegie
    • 2
  • John D. Scott
    • 1
  1. 1.Department of Pharmacology, Howard Hughes Medical InstituteUniversity of WashingtonSeattleUSA
  2. 2.Department of PharmacologyUniversity of Illinois at ChicagoChicagoUSA