Skip to main content
Log in

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

  • Published:
Plant Molecular Biology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • Braselmann, S. and McCormick, F. 1995. Bcr and Raf form a complex in vivo via 14-3-3 proteins. EMBO J. 14: 4839-4848.

    PubMed  Google Scholar 

  • Busk, P.K. and Pagès, M. 1998. Regulation of abscisic acid-induced transcription. Plant Mol. Biol. 37: 425-435.

    PubMed  Google Scholar 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • de Boer, B. 1997. Fusicoccin: a key tomultiple 14-3-3 locks? Trends Plant. Sci. 2: 60-66.

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • Ferl, R.J. 1996. 14-3-3 proteins and signal transduction. Annu. Rev. Plant. Physiol. Plant Mol. Biol. 47: 49-73.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • MacKintosh, C. 1998. Regulation of plant nitrate assimilation: from ecophysiology to brain proteins. New Phytol. 139: 153-159.

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Palmgren, M.G., Fuglsang, A.T. and Jahn, T. 1998. Deciphering the role of 14-3-3 proteins. Exp. Biol. Online 3: 4 (http: //www.link.springer.de/link/service/journals/00898/bibs/8003001 /80030004.htm).

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Roberts, M.R. and Bowles, D.J. 1999. Fusicoccin, 14-3-3 proteins, and defence responses in tomato plants. Plant Physiol. 119: 1243-1250.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Sayle, R.A. and Millner-White, E.J. 1995. RASMOL: biomolecular graphics for all. Trends Biochem. Sci. 20: 374-376.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Sehnke, P.C. and Ferl, R.J. 1996. Plant metabolism: enzyme regulation by 14-3-3 proteins. Curr. Biol. 6: 1403-1405.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Wang, W. and Shakes, D. 1996. Molecular evolution of the 14-3-3 protein family. J. Mol. Evol. 43: 384-398.

    PubMed  Google Scholar 

  • 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 

  • Wu, K., Rooney, M.F. and Ferl, R.J. 1997. The Arabidopsis 14-3-3 multigene family. Plant Physiol. 114: 1421-1431.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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).

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Finnie, C., Borch, J. & Collinge, D.B. 14-3-3 proteins: eukaryotic regulatory proteins with many functions. Plant Mol Biol 40, 545–554 (1999). https://doi.org/10.1023/A:1006211014713

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006211014713

Navigation