Plant Molecular Biology

, Volume 40, Issue 4, pp 545–554 | Cite as

14-3-3 proteins: eukaryotic regulatory proteins with many functions

  • Christine Finnie
  • Jonas Borch
  • David B. Collinge


The enigmatically named 14-3-3 proteins have been the subject of considerable attention in recent years since they have been implicated in the regulation of diverse physiological processes, in eukaryotes ranging from slime moulds to higher plants. In plants they have roles in the regulation of the plasma membrane H+-ATPase and nitrate reductase, among others. Regulation of target proteins is achieved through binding of 14-3-3 to short, often phosphorylated motifs in the target, resulting either in its activation (e.g. H+-ATPase), inactivation (e.g. nitrate reductase) or translocation (although this function of 14-3-3 proteins has yet to be demonstrated in plants). The native 14-3-3 proteins are homo- or heterodimers and, as each monomer has a binding site, a dimer can potentially bind two targets, promoting their association. Alternatively, target proteins may have more than one 14-3-3-binding site. In this mini review, we present a synthesis of recent results from plant 14-3-3 research and, with reference to known 14-3-3-binding motifs, suggest further subjects for research.

binding motif fusicoccin G-box binding phosphorylation protein–protein interaction signal transduction 


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  1. Aitken, A., Collinge, D.B., van Heusden, B.P.H., Isobe, T., Roseboom, P.H., Rosenfeld, G. and Soll, J. 1992. 14-3-3 proteins: a highly conserved, widespread family of eukaryotic proteins. Trends Biochem. Sci. 17: 498-501.PubMedGoogle Scholar
  2. Andrews, R.K., Harris, S.J., McNally, T., Berndt, M.C. 1998. Binding of purified 14-3-3 signaling protein to discrete amino acid sequences within the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex. Biochemistry 37: 638-647.PubMedGoogle Scholar
  3. Athwal, G.S., Huber, J.L. and Huber, S.C. 1998a. Biological significance of divalent metal ion binding to 14-3-3 proteins in relationship to nitrate reductase inactivation. Plant Cell Physiol. 39: 1065-1072.PubMedGoogle Scholar
  4. Athwal, G.S., Huber, J.L. and Huber, S.C. 1998b. Phosphorylated nitrate reductase and 14-3-3 proteins. Site of interaction, effects of ions, and evidence for an AMP-binding site on 14-3-3 proteins. Plant Physiol. 118: 1041-1048.PubMedGoogle Scholar
  5. Bachmann, M., Huber, J.L., Athwal, G.S., Wu, K., Ferl, R.J. and Huber, S.C. 1996a. 14-3-3 proteins associate with the regulatory phosphorylation site of spinach leaf nitrate reductase in an isoform-specific manner and reduce dephosphorylation of Ser-543 by endogenous protein phosphatases. FEBS Lett. 398: 26-30.PubMedGoogle Scholar
  6. Bachmann, M., Shirashi, N., Campbell, W.H., Yoo, B.-C., Harmon, A.C. and Huber, S.C. 1996b. Identification of Ser-543 as the major regulatory phosphorylation site in spinach leaf nitrate reductase. Plant Cell 8: 505-517.PubMedGoogle Scholar
  7. Baunsgaard, L., Fuglsang, A.T., Jahn, T., Korthout, H.A.A.J., de Boer, A.H. and Palmgren, M.G. 1998. The 14-3-3 protein associates with the plasma membrane HC-ATPase to generate a fusicoccin binding complex and a fusicoccin responsive system. Plant J. 13: 661-671.PubMedGoogle Scholar
  8. Bernstein, F.C., Koetzle, T.F., Williams, G.J.B., Meyer, E.F., Brice, M.D., Rodgers, J.R., Kennard, O., Shimanouchi, T. and Tasumi, M. 1997. The protein data bank: a computer based archival file for macromolecular structures. J. Mol. Biol. 112: 535-542.Google Scholar
  9. Bihn, E.A., Paul, A.L., Wang, S.W., Erdos, G.W. and Ferl, R.J. 1997. Localization of 14-3-3 proteins in the nuclei of arabidopsis and maize. Plant J. 12: 1439-1445.Google Scholar
  10. Blatt, M.R. and Clint, G.M. 1989. Mechanisms of fusicoccin action: kinetic modification and inactivation of KC channels in guard cells. Planta 178: 509-523.Google Scholar
  11. Brandt, J., Thordal-Christensen, H., Vad, K., Gregersen, P.L. and Collinge, D.B. 1992. A pathogen induced gene of barley encodes a protein showing high similarity to a protein kinase regulator. Plant J. 2: 815-820.PubMedGoogle Scholar
  12. Braselmann, S. and McCormick, F. 1995. Bcr and Raf form a complex in vivo via 14-3-3 proteins. EMBO J. 14: 4839-4848.PubMedGoogle Scholar
  13. Busk, P.K. and Pagès, M. 1998. Regulation of abscisic acid-induced transcription. Plant Mol. Biol. 37: 425-435.PubMedGoogle Scholar
  14. Camoni, L., Fullone, M.R., Marra, M. and Aducci, P. 1998a. The plasma membrane HC-ATPase from maize roots is phosphorylated in the C-terminal domain by a calcium-dependent protein kinase. Physiol. Plant. 104: 549-555.Google Scholar
  15. Camoni, L., Harper, J.F. and Palmgren, M.G. 1998b. 14-3-3 proteins activate a plant calcium dependent protein kinase (CDPK). FEBS Lett. 430: 381-384.PubMedGoogle Scholar
  16. Daugherty, C.J., Rooney, M.F., Miller, P.W. and Ferl, R.J. 1996. Molecular organization and tissue-specific expression of an arabidopsis 14-3-3 gene. Plant Cell 8: 1239-1248.PubMedGoogle Scholar
  17. de Boer, B. 1997. Fusicoccin: a key tomultiple 14-3-3 locks? Trends Plant. Sci. 2: 60-66.Google Scholar
  18. de Vetten, N.C. and Ferl, R.J. 1992. A maize protein associated with the G-box binding complex has homology to brain regulatory proteins. Plant Cell 4: 1295-1307.PubMedGoogle Scholar
  19. Douglas, P., Moorhead, G., Hong, Y., Morrice, N. and MacKintosh, C. 1998. Purification of a nitrate reductase kinase from Spinacea oleracea leaves, and its identification as a calmodulin domain protein kinase. Planta 206: 435-442.PubMedGoogle Scholar
  20. Douglas, P., Morrice, N. and MacKintosh, C. 1995. Identification of a regulatory phosphorylation site in the hinge 1 region of nitrate reductase from spinach (Spinacea oleracea) leaves. FEBS Lett. 377: 113-117.PubMedGoogle Scholar
  21. Douglas, P., Pigaglio, E., Ferrer, A., Halfords, N.G. and Mac-Kintosh, C. 1997. Three spinach nitrate reductase kinases that are regulated by reversible phosphorylation and Ca2C ions. Biochem. J. 325: 101-109.PubMedGoogle Scholar
  22. Faris, J.D., Li, W.L., Liu, D.J., Chen, P.D. and Gill, B.S. 1999. Candidate gene analysis of quantitative disease resistance in wheat. Theor. Appl. Genet. 98: 219-225.Google Scholar
  23. Ferl, R.J. 1996. 14-3-3 proteins and signal transduction. Annu. Rev. Plant. Physiol. Plant Mol. Biol. 47: 49-73.PubMedGoogle Scholar
  24. Fullone, M.R., Visconti, S., Marra, M., Fogliano, V. and Aducci, P. 1998. Fusicoccin effect on the in vitro interaction between plant 14-3-3 proteins and plasma membrane HC-ATPase. J. Biol. Chem. 273: 7698-7702.PubMedGoogle Scholar
  25. Gregersen, P.L., Thordal-Christensen, H., Förster, H. and Collinge, D.B. 1997. Differential gene transcript accumulation in barley leaf epidermis and mesophyll in response to attack by Blumeria graminis f.sp. hordei. Physiol. Mol. Plant. Path. 51: 85-97.Google Scholar
  26. Hess, W.R., Golz, R. and Börner, T. 1998. Analysis of randomly selected cDNAs reveals the expression of stress-and defencerelated genes in the barley mutant albostrians. Plant Sci. 133: 191-201.Google Scholar
  27. Hill, A., Nantel, A., Rock, C.D. and Quatrano, R.S. 1996. A conserved domain of the viviparous-1 gene product enhances the DNA binding activity of the bZIP protein EmBP-1 and other transcription factors. J. Biol. Chem. 271: 3366-3374.PubMedGoogle Scholar
  28. Huber, S.C. and Huber, J.L. 1996. Role and regulation of sucrosephosphate synthase in higher plants. Annu. Rev. Plant. Physiol. Plant Mol. Biol. 47: 431-444.PubMedGoogle Scholar
  29. Jahn, T., Fuglsang, A.T., Olsson, A., Brüntrup, I.M., Collinge, D.B., Volkmann, D., Sommarin, M., Palmgren, M.G. and Larsson, C. 1997. The 14-3-3 protein interacts directly with the C-terminal region of the plant plasma membrane HC-ATPase. Plant Cell 9: 1805-1814.PubMedGoogle Scholar
  30. Jones, D.H., Ley, S. and Aitken, A. 1995. Isoforms of 14-3-3 protein can form homo-and heterodimers in vivo and in vitro: implications for function as adapter proteins. FEBS Lett. 368: 55-58.PubMedGoogle Scholar
  31. Kanamaru, K., Wang, R., Su, W. and Crawford, N.M. 1999. Ser-534 in the hinge 1 region of Arabidopsis nitrate reductase is conditionally required for binding of 14-3-3 proteins and in vitro inhibition. J. Biol. Chem. 274: 4160-4165.PubMedGoogle Scholar
  32. Korthout, H.A.A.J. and de Boer, A.H. 1994. A fusicoccin binding protein belongs to the family of 14-3-3 brain protein homologs. Plant Cell 6: 1682-1692.Google Scholar
  33. Liu, D., Bienkowska, J., Petosa, C., Collier, R.J., Fu, H. and Liddington, R. 1995. Crystal structure of the zeta isoform of the 14-3-3 protein. Nature 376: 191-194.PubMedGoogle Scholar
  34. Lopez-Girona, A., Furnari, B., Mondesert, O. and Russell, P. 1999. Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein. Nature 397: 172-175.PubMedGoogle Scholar
  35. Lu, G., DeLisle, A., de Vetten, N.C. and Ferl, R.J. 1992. Brain proteins in plants: an Arabidopsis homolog to neurotransmitter pathway activators is part of a DNA binding complex. Proc. Natl. Acad. Sci. USA 89: 11490-11494.PubMedGoogle Scholar
  36. Lu, G.H., Sehnke, P.C. and Ferl, R.J. 1994. Phosphorylation and calcium-binding properties of an Arabidopsis GF14 brain protein homolog. Plant Cell 6: 501-510.PubMedGoogle Scholar
  37. Luo, Z., Zhang, X., Rapp, U. and Avruch, J. 1995. Identification of the 14.3.3 domains important for self-association and Raf binding. J. Biol. Chem. 270: 23681-23687.PubMedGoogle Scholar
  38. MacKintosh, C. 1998. Regulation of plant nitrate assimilation: from ecophysiology to brain proteins. New Phytol. 139: 153-159.Google Scholar
  39. MacKintosh, C., Douglas, P. and Lillo, C. 1995. Identification of a protein that inhibits the phosphorylated form of nitrate reductase from spinach leaves. Plant Physiol. 107: 451-457.PubMedGoogle Scholar
  40. Markiewicz, E., Wiczy´nski, G., Rzepecki, R., Kulma, A. and Szopa, J 1996. The 14-3-3 protein binds to the nuclear matrix endonuclease and has a possible function in the control of plant senescence. Cell Mol. Biol. Lett. 1: 391-415.Google Scholar
  41. McMichael, R.W., Klein, R.R., Salvucci, M.E. and Huber, S.C. 1993. Identification of the major regulatory phosphorylation site in sucrose phosphate synthase. Arch Biochem. Biophys. 307: 248-252.PubMedGoogle Scholar
  42. Moore, B.W. and Perez, V.J. 1967. Specific acidic proteins of the nervous system. In: F.D. Carlson (Ed.), Physiological and Biochemical Aspects of Nervous Integration, Prentice-Hall, Englewood Cliffs, NJ, pp. 343-359.Google Scholar
  43. Moorhead, G., Douglas, P., Cotelle, V., Harthill, J., Morrice, N., Meek, S., Deiting, U., Stitt, M., Scarabel, M., Aitken, A. and Mackintosh, C. 1999. Phosphorylation-dependent interactions between enzymes of plant metabolism and 14-3-3 proteins. Plant J. 18: 1-12.Google Scholar
  44. Moorhead, G., Douglas, P., Morrice, N., Scarabel, M., Aitken, A. and MacKintosh, C. 1996. Phosphorylated nitrate reductase from spinach leaves is inhibited by 14-3-3 proteins and activated by fusicoccin. Curr. Biol. 6: 1104-1113.PubMedGoogle Scholar
  45. Muslin, A.J., Tanner, J.W., Allen, P.M. and Shaw, A.S. 1996. Interaction of 14-3-3 with signalling proteins is mediated by the recognition of phosphoserine. Cell 84: 889-897.CrossRefPubMedGoogle Scholar
  46. Oecking, C., Eckershorn, C. and Weiler, E.W. 1994. The fusicoccin receptor of plants is a member of the 14-3-3 superfamily of eukaryotic regulatory proteins. FEBS Lett. 352: 163-166.PubMedGoogle Scholar
  47. Oecking, C. and Hagemann, K. 1999. Association of 14-3-3 proteins with the C-terminal autoinhibitory domain of the plant plasmamembrane HC-ATPase generates a fusicoccin-binding complex. Planta 207: 480-482.Google Scholar
  48. Oecking, C., Piotrowski, M., Hagemeier, J. and Hagemann, K. 1997. Topology and target interaction of the fusicoccin-binding 14-3-3 homologs of Commelina communis. Plant J. 12: 441-453.Google Scholar
  49. Olivari, C., Meanti, C., De Michelis, M.I. and Rasi-Caldogno, F. 1998. Fusicoccin binding to its plasma membrane receptor and the activation of the plasma-membrane HC-ATPase. IV. Fusicoccin induces the association between the plasma membrane HC-ATPase and the fusicoccin receptor. Plant Physiol. 116: 529-537.PubMedGoogle Scholar
  50. Olsson, A., Svennelid, F., Ek, B., Sommarin, M. and Larsson, C. 1998. A phosphothreonine residue at the C-terminal end of the plasma membrane HC-ATPase is protected by fusicoccininduced 14-3-3 binding. Plant Physiol. 118: 551-555.PubMedGoogle Scholar
  51. Palmgren, M.G., Fuglsang, A.T. and Jahn, T. 1998. Deciphering the role of 14-3-3 proteins. Exp. Biol. Online 3: 4 (http: // /80030004.htm).Google Scholar
  52. Palmgren, M.G., Larsson, C. and Sommarin, M. 1990. Proteolytic activation of the plant plasma membrane HC-ATPase by removal of a terminal segment. J. Biol. Chem. 265: 13423-13426.PubMedGoogle Scholar
  53. Petosa, C., Masters, S.C., Bankston, L.A., Pohl, J., Wang, B., Fu, H. and Liddington, R.C. 1998. 14-3-3 binds a phosphorylated peptide via its conserved amphipathic groove. J. Biol. Chem. 273: 16305-16310.PubMedGoogle Scholar
  54. Piotrowski, M., Morsomme, P., Boutry, M. and Oecking, C. 1998. Complementation of the Saccharomyces cerevisiae plasma membrane HC-ATPase by a plant HC-ATPase generates a highly abundant fusicoccin binding site. J. Biol. Chem. 273: 30018-30023.PubMedGoogle Scholar
  55. Piotrowski, M. and Oecking, C. 1998. Five new 14-3-3 isoforms from Nicotiana tabacum L.: implications for the phylogeny of plant 14-3-3 proteins. Planta 204: 127-130.PubMedGoogle Scholar
  56. Roberts, M.R. and Bowles, D.J. 1999. Fusicoccin, 14-3-3 proteins, and defence responses in tomato plants. Plant Physiol. 119: 1243-1250.PubMedGoogle Scholar
  57. Saalbach, G., Schwerdel, M., Natura, G., Buschmann, P., Christov, V. and Dahse, I. 1997. Over-expression of plant 14-3-3 proteins in tobacco: enhancement of the plasmalemma KC conductance of mesophyll cells. FEBS Lett. 413: 294-298.PubMedGoogle Scholar
  58. Sayle, R.A. and Millner-White, E.J. 1995. RASMOL: biomolecular graphics for all. Trends Biochem. Sci. 20: 374-376.PubMedGoogle Scholar
  59. Schaller, A. and Oecking, C. 1999. Modulation of plasma membrane HC-ATPase activity differentially activates wound and pathogen defense responses in tomato plants. Plant Cell 11: 1-10.PubMedGoogle Scholar
  60. Schultz, T.F., Medina, J., Hill, A. and Quatrano, R.S. 1998. 14-3-3 proteins are part of an abscisic acid-VIVIPAROUS1 (VP1) response complex in the Em promoter and interact with VP1 and EmBP1. Plant Cell 10: 837-847.PubMedGoogle Scholar
  61. Seehaus, K. and Tenhaken, R. 1998. Cloning of genes by mRNA differential display induced during the hypersensitive reaction of soybean after inoculation with Pseudomonas syringae pv. glycinea. Plant Mol. Biol. 38: 1225-1234.PubMedGoogle Scholar
  62. Sehnke, P.C. and Ferl, R.J. 1996. Plant metabolism: enzyme regulation by 14-3-3 proteins. Curr. Biol. 6: 1403-1405.PubMedGoogle Scholar
  63. Su,W., Huber, S.C. and Crawford, N.M. 1996. Identification in vitro of a post-translational regulatory site in the hinge 1 region of Arabidopsis nitrate reductase. Plant Cell 8: 519-527.PubMedGoogle Scholar
  64. Toroser, D., Athwal, G.S. and Huber, S.C. 1998. Site-specific regulatory interaction between spinach leaf sucrose-phosphate synthase and 14-3-3 proteins. FEBS Lett. 435: 110-114.PubMedGoogle Scholar
  65. Toroser, D. and Huber, S.C. 1997. Protein phosphorylation as a mechanism for osmotic-stress activation of sucrose-phosphate synthase in spinach leaves. Plant Physiol. 114: 947-955.PubMedGoogle Scholar
  66. Toroser, D., McMichael, R., Krause, K.P., Kurreck, J., Sonnewald, U., Stitt, M. and Huber, S.C. 1999. Site-directed mutagenesis of serine 158 demonstrates its role in spinach leaf sucrose-phosphate synthase modulation. Plant J. 17: 407-413.Google Scholar
  67. Tzivion, G., Luo, Z. and Avruch, J. 1998. A dimeric 14-3-3 protein is an essential cofactor for Raf kinase activity. Nature 394: 88-92.Google Scholar
  68. Vera-Estrella, R., Barkla, B., Higgins, V.J. and Blumwald, E. 1994. Plant defense response to fungal pathogens: activation of host plasma membrane HC-ATPase by elicitor-induced enzyme dephosphorylation. Plant Physiol. 104: 209-215.PubMedGoogle Scholar
  69. Wang, H., Zhang, L., Liddington, R. and Fu, H. 1998. Mutations in the hydrophobic surface of an amphipathic groove of 14-3-3. disrupt its interaction with Raf-1 kinase. J. Biol. Chem. 273: 16297-16304.PubMedGoogle Scholar
  70. Wang, W. and Shakes, D. 1996. Molecular evolution of the 14-3-3 protein family. J. Mol. Evol. 43: 384-398.PubMedGoogle Scholar
  71. Wiczy´nski, G., Kulma, A. and Szopa, J. 1998. the expression of 14-3-3 isoforms in potato is developmentally regulated. J. Plant. Physiol. 153: 118-126.Google Scholar
  72. Wu, K., Rooney, M.F. and Ferl, R.J. 1997. The Arabidopsis 14-3-3 multigene family. Plant Physiol. 114: 1421-1431.PubMedGoogle Scholar
  73. Wu, K., Lu, G., Sehnke, P. and Ferl, R.J. 1997. The heterologous interactions among plant 14-3-3 proteins and identification of regions that are important for dimerization. Arch. Biochem. Biophys. 339: 2-8.PubMedGoogle Scholar
  74. Xiao, B., Smerdon, S.J., Jones, D.H., Dodson, G.G., Soneji, Y., Aitken, A. and Gamblin, S.J. 1995. Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways. Nature 376: 188-191.PubMedGoogle Scholar
  75. Yaffe, M.B., Rittinger, K., Volinia, S., Caron, P.R., Aitken, A., Leffers, H., Gamblin, S.J., Smerdon, S.J. and Cantley, L.C. 1997. The structural basis for 14-3-3:phosphopeptide binding specificity. Cell 91: 961-971.PubMedGoogle Scholar
  76. Zhang, H., Wang, J. and Goodman, H.M. 1997a. An Arabidopsis gene encoding a putative 14-3-3-interacting protein, caffeic acid/5-hydroxyferulic acid O-methyl transferase. Biochim. Biophys. Acta 1353: 199-202 (1997).Google Scholar
  77. Zhang, H., Wang, J., Nickel, U., Allen, R.D. and Goodman, H.M. 1997b. Cloning and expression of an Arabidopsis gene encoding a putative peroxisomal ascorbate peroxidase. Plant Mol. Biol. 34: 967-971.PubMedGoogle Scholar
  78. Zhang, L., Wang, H., Liu, D., Liddington, R. and Fu, H. 1997c. Raf-1 kinase and Exoenzyme-S interact with 14-3-3 through a common site involving lysine 49. J. Biol. Chem. 272: 13717-13724.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Christine Finnie
    • 1
  • Jonas Borch
    • 1
  • David B. Collinge
    • 1
  1. 1.Plant Pathology Section, Department of Plant BiologyThe Royal Veterinary and Agricultural University, Thorvaldsensvej 40Frederiksberg C, CopenhagenDenmark

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