Home LiteratureArticle Details
PMID: 16377759 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Arabidopsis TARGET OF RAPAMYCIN interacts with RAPTOR, which regulates the activity of S6 kinase in response to osmotic stress signals.

The Plant cell ·Vol. 18 ·No. 2 ·2006-02-00 ·Pages 477-90

Mahfouz MM, Kim S, Delauney AJ, Verma DP

Abstract

TARGET OF RAPAMYCIN (TOR) kinase controls many cellular functions in eukaryotic cells in response to stress and nutrient availability and was shown to be essential for embryonic development in Arabidopsis thaliana. We demonstrated that Arabidopsis RAPTOR1 (a TOR regulatory protein) interacts with the HEAT repeats of TOR and that RAPTOR1 regulates the activity of S6 kinase (S6K) in response to osmotic stress. RAPTOR1 also interacts in vivo with Arabidopsis S6K1, a putative substrate for TOR. S6K1 fused to green fluorescent protein and immunoprecipitated from tobacco (Nicotiana tabacum) leaves after transient expression was active in phosphorylating the Arabidopsis ribosomal S6 protein. The catalytic domain of S6K1 could be phosphorylated by Arabidopsis 3-phosphoinositide-dependent protein kinase-1 (PDK1), indicating the involvement of PDK1 in the regulation of S6K. The S6K1 activity was sensitive to osmotic stress, while PDK1 activity was not affected. However, S6K1 sensitivity to osmotic stress was relieved by co-overexpression of RAPTOR1. Overall, these observations demonstrated the existence of a functional TOR kinase pathway in plants. However, Arabidopsis seedlings do not respond to normal physiological levels of rapamycin, which appears to be due its inability to bind to the Arabidopsis homolog of FKBP12, a protein that is essential for the binding of rapamycin with TOR. Replacement of the Arabidopsis FKBP12 with the human FKBP12 allowed rapamycin-dependent interaction with TOR. Since homozygous mutation in TOR is lethal, it suggests that this pathway is essential for integrating the stress signals into the growth regulation.

MeSH Terms
3-Phosphoinositide-Dependent Protein Kinases Amino Acid Motifs Amino Acid Sequence Arabidopsis/metabolism Arabidopsis Proteins/metabolism Exons/genetics Gene Expression Gene Expression Regulation, Plant Molecular Sequence Data Osmotic Pressure Phosphatidylinositol 3-Kinases Phosphorylation Plants, Genetically Modified/anatomy & histology Protein Binding Protein Serine-Threonine Kinases/metabolism Protein Structure, Tertiary Protein Transport Ribosomal Protein S6 Kinases/chemistry,metabolism Signal Transduction Tacrolimus Binding Protein 1A/metabolism
Chemicals
Arabidopsis Proteins Raptor1 protein, Arabidopsis TOR protein, Arabidopsis 3-Phosphoinositide-Dependent Protein Kinases PDPK1 protein, human Protein Serine-Threonine Kinases Ribosomal Protein S6 Kinases Tacrolimus Binding Protein 1A
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mahfouz Magdy M
Department of Molecular Genetics and Plant Biotechnology Center, The Ohio State University, Columbus, Ohio 43210, USA.
Kim Sunghan
Delauney Ashton J
Verma Desh Pal S
References (70)
70 references, click to expand
  1. Phosphorylation sites in the autoinhibitory domain participate in p70(s6k) activation loop phosphorylation.
    J Biol Chem. 1998 Jun 12;273(24):14845-52 PMID: 9614086
  2. Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and degradation.
    Curr Opin Genet Dev. 1999 Feb;9(1):49-54 PMID: 10072357
  3. Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4438-42 PMID: 10200280
  4. Characterisation of a plant 3-phosphoinositide-dependent protein kinase-1 homologue which contains a pleckstrin homology domain.
    FEBS Lett. 1999 May 28;451(3):220-6 PMID: 10371193
  5. Osmotic stress inhibits p70/85 S6 kinase through activation of a protein phosphatase.
    J Biol Chem. 1999 Aug 27;274(35):24731-6 PMID: 10455142
  6. MAF1, a novel plant protein interacting with matrix attachment region binding protein MFP1, is located at the nuclear envelope.
    Plant Cell. 1999 Sep;11(9):1755-68 PMID: 10488241
  7. Multiple roles of Tap42 in mediating rapamycin-induced transcriptional changes in yeast.
    Mol Cell. 2003 Jun;11(6):1467-78 PMID: 12820961
  8. Regulated phosphorylation of 40S ribosomal protein S6 in root tips of maize.
    Plant Physiol. 2003 Aug;132(4):2086-97 PMID: 12913163
  9. TOR action in mammalian cells and in Caenorhabditis elegans.
    Curr Top Microbiol Immunol. 2004;279:115-38 PMID: 14560955
  10. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function.
    Genes Cells. 2004 Apr;9(4):359-66 PMID: 15066126
  11. Phytohormones participate in an S6 kinase signal transduction pathway in Arabidopsis.
    Plant Physiol. 2004 Apr;134(4):1527-35 PMID: 15064379
  12. The TOR pathway: a target for cancer therapy.
    Nat Rev Cancer. 2004 May;4(5):335-48 PMID: 15122205
  13. Plant growth: the translational connection.
    Biochem Soc Trans. 2004 Aug;32(Pt 4):581-4 PMID: 15270681
  14. Purification of a hepatic S6 kinase from cycloheximide-treated Rats.
    J Biol Chem. 1989 Aug 15;264(23):13825-33 PMID: 2760046
  15. A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase.
    Nature. 1989 Oct 26;341(6244):758-60 PMID: 2477715
  16. Hormonally inducible phosphorylation of a nuclear pool of ribosomal protein S6.
    J Biol Chem. 1990 Mar 15;265(8):4321-5 PMID: 2106518
  17. Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a peptidyl-prolyl cis-trans isomerase related to human FK506-binding protein.
    Mol Cell Biol. 1991 Mar;11(3):1718-23 PMID: 1996117
  18. Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex.
    Science. 1991 May 10;252(5007):839-42 PMID: 1709302
  19. Eukaryotic proteins expressed in Escherichia coli: an improved thrombin cleavage and purification procedure of fusion proteins with glutathione S-transferase.
    Anal Biochem. 1991 Feb 1;192(2):262-7 PMID: 1852137
  20. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast.
    Science. 1991 Aug 23;253(5022):905-9 PMID: 1715094
  21. Improved method for high efficiency transformation of intact yeast cells.
    Nucleic Acids Res. 1992 Mar 25;20(6):1425 PMID: 1561104
  22. Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases.
    Cell. 1992 Jun 26;69(7):1227-36 PMID: 1377606
  23. Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase.
    Science. 1992 Aug 14;257(5072):973-7 PMID: 1380182
  24. Phosphorylation independent activation of human cyclin-dependent kinase 2 by cyclin A in vitro.
    Mol Biol Cell. 1993 Jan;4(1):79-92 PMID: 8443411
  25. Elongation factor-1 alpha mRNA is selectively translated following mitogenic stimulation.
    J Biol Chem. 1994 Feb 11;269(6):4367-72 PMID: 8308006
  26. atpk1, a novel ribosomal protein kinase gene from Arabidopsis. II. Functional and biochemical analysis of the encoded protein.
    J Biol Chem. 1994 Jul 1;269(26):17593-9 PMID: 8021267
  27. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex.
    Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12574-8 PMID: 7809080
  28. Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands.
    EMBO J. 1994 Dec 15;13(24):5944-57 PMID: 7529175
  29. Two genes that encode ribosomal-protein S6 kinase homologs are induced by cold or salinity stress in Arabidopsis thaliana.
    FEBS Lett. 1995 Jan 23;358(2):199-204 PMID: 7828736
  30. Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue.
    Proc Natl Acad Sci U S A. 1995 May 23;92(11):4947-51 PMID: 7539137
  31. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification.
    FASEB J. 1995 May;9(8):576-96 PMID: 7768349
  32. A novel FK506 binding protein can mediate the immunosuppressive effects of FK506 and is associated with the cardiac ryanodine receptor.
    J Biol Chem. 1995 Nov 3;270(44):26511-22 PMID: 7592869
  33. The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain.
    EMBO J. 1995 Nov 1;14(21):5279-87 PMID: 7489717
  34. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha.
    Curr Biol. 1997 Apr 1;7(4):261-9 PMID: 9094314
  35. Direct interaction of gbetagamma with a C-terminal gbetagamma-binding domain of the Ca2+ channel alpha1 subunit is responsible for channel inhibition by G protein-coupled receptors.
    Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8866-71 PMID: 9238069
  36. The modular phosphorylation and activation of p70s6k.
    FEBS Lett. 1997 Jun 23;410(1):78-82 PMID: 9247127
  37. TOR signalling and control of cell growth.
    Curr Opin Cell Biol. 1997 Dec;9(6):782-7 PMID: 9425342
  38. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro.
    Curr Biol. 1998 Jan 15;8(2):69-81 PMID: 9427642
  39. Phosphorylation and activation of p70s6k by PDK1.
    Science. 1998 Jan 30;279(5351):707-10 PMID: 9445476
  40. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1.
    Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1432-7 PMID: 9465032
  41. Ribosomal S6 kinase signaling and the control of translation.
    Exp Cell Res. 1999 Nov 25;253(1):100-9 PMID: 10579915
  42. The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors.
    Nature. 1999 Dec 9;402(6762):689-92 PMID: 10604478
  43. Random GFP::cDNA fusions enable visualization of subcellular structures in cells of Arabidopsis at a high frequency.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3718-23 PMID: 10737809
  44. An encore for ribosome biogenesis in the control of cell proliferation.
    Nat Cell Biol. 2000 May;2(5):E71-2 PMID: 10806485
  45. AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation.
    Annu Rev Biochem. 1999;68:965-1014 PMID: 10872470
  46. Specificity and mechanism of action of some commonly used protein kinase inhibitors.
    Biochem J. 2000 Oct 1;351(Pt 1):95-105 PMID: 10998351
  47. Floral spray transformation can efficiently generate Arabidopsis transgenic plants.
    Transgenic Res. 2000 Dec;9(6):471-6 PMID: 11206976
  48. The TOR kinases link nutrient sensing to cell growth.
    J Biol Chem. 2001 Mar 30;276(13):9583-6 PMID: 11266435
  49. Cloning and characterization of a nuclear S6 kinase, S6 kinase-related kinase (SRK); a novel nuclear target of Akt.
    Oncogene. 1999 Sep 9;18(36):5115-9 PMID: 10490848
  50. An Arabidopsis homolog of RAPTOR/KOG1 is essential for early embryo development.
    Biochem Biophys Res Commun. 2005 Jan 28;326(4):844-50 PMID: 15607746
  51. TOR signaling: an odyssey from cellular stress to the cell growth machinery.
    Curr Biol. 2005 Feb 22;15(4):R139-41 PMID: 15723787
  52. The Arabidopsis Mei2 homologue AML1 binds AtRaptor1B, the plant homologue of a major regulator of eukaryotic cell growth.
    BMC Plant Biol. 2005 Feb 21;5:2 PMID: 15720729
  53. The Arabidopsis AtRaptor genes are essential for post-embryonic plant growth.
    BMC Biol. 2005;3:12 PMID: 15845148
  54. Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002.
    EMBO J. 1996 Oct 1;15(19):5256-67 PMID: 8895571
  55. Protein kinase C phosphorylates ribosomal protein S6 kinase betaII and regulates its subcellular localization.
    Mol Cell Biol. 2003 Feb;23(3):852-63 PMID: 12529391
  56. Tor signalling in bugs, brain and brawn.
    Nat Rev Mol Cell Biol. 2003 Feb;4(2):117-26 PMID: 12563289
  57. An enhanced transient expression system in plants based on suppression of gene silencing by the p19 protein of tomato bushy stunt virus.
    Plant J. 2003 Mar;33(5):949-56 PMID: 12609035
  58. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif.
    J Biol Chem. 2003 May 2;278(18):15461-4 PMID: 12604610
  59. A cell plate-specific callose synthase and its interaction with phragmoplastin.
    Plant Cell. 2001 Apr;13(4):755-68 PMID: 11283334
  60. The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB.
    EMBO J. 2001 Aug 15;20(16):4380-90 PMID: 11500365
  61. Mammalian TOR: a homeostatic ATP sensor.
    Science. 2001 Nov 2;294(5544):1102-5 PMID: 11691993
  62. The TOR signal transduction cascade controls cellular differentiation in response to nutrients.
    Mol Biol Cell. 2001 Dec;12(12):4103-13 PMID: 11739804
  63. Identification of a conserved motif required for mTOR signaling.
    Curr Biol. 2002 Apr 16;12(8):632-9 PMID: 11967149
  64. Expression and disruption of the Arabidopsis TOR (target of rapamycin) gene.
    Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6422-7 PMID: 11983923
  65. GATEWAY vectors for Agrobacterium-mediated plant transformation.
    Trends Plant Sci. 2002 May;7(5):193-5 PMID: 11992820
  66. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.
    Cell. 2002 Jul 26;110(2):163-75 PMID: 12150925
  67. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.
    Cell. 2002 Jul 26;110(2):177-89 PMID: 12150926
  68. Identification of TOR signaling complexes: more TORC for the cell growth engine.
    Cell. 2002 Oct 4;111(1):9-12 PMID: 12372295
  69. Mitogen-activated protein kinase signaling in postgermination arrest of development by abscisic acid.
    Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15812-7 PMID: 12434021
  70. A heat-sensitive Arabidopsis thaliana kinase substitutes for human p70s6k function in vivo.
    Mol Cell Biol. 1998 Apr;18(4):2038-44 PMID: 9528776
Article Info
Journal
The Plant cell
Abbr.
Plant Cell
ISSN
1040-4651
DOI
10.1105/tpc.105.035931
Published
2006-02-00
Epub
2005-00-23
Pages
477-90
Language
English
Region
England
NLM ID
9208688
PMCID
PMC1356553
Subset
IM
External Links
PubMed source DOI: 10.1105/tpc.105.035931 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2