CoChat
Sign Up
Cited by 59Alzheimer's disease research and treatmentsMicrotubule and mitosis dynamicsProtein Kinase Regulation and GTPase Signaling

Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) Increases Neurite Formation through Microtubule Depolymerization by SGK1 and by SGK1 Phosphorylation of tau

Open access
Yang, Ying C., Lin, Cheng H., Lee, Eminy H. Y.·2006·Molecular and Cellular Biology
DOI 10.1128/mcb.01017-06PMC PMC1636775
Open this paper in CoChat — free account

Abstract

Serum- and glucocorticoid-inducible kinase 1 (SGK1) is a member of the Ser/Thr protein kinase family that regulates a variety of cell functions. Recently, SGK1 was shown to increase dendritic growth but the mechanism underlying the increase is unknown. Here we demonstrated that SGK1 increased the neurite formation of cultured hippocampal neurons through microtubule (MT) depolymerization via two distinct mechanisms. First, SGK1 directly depolymerized MTs. In vitro MT depolymerization experiments revealed that SGK1, especially N-truncated SGK1, directly disassembled self-polymerized MTs and taxol-stabilized MTs in a dose-dependent and ATP-independent manner. The transfection of sgk1 to HeLa cells also inhibited MT assembly in vivo. Second, SGK1 indirectly depolymerized MTs through the phosphorylation of tau at Ser214. An in vitro kinase assay revealed that active SGK1 phosphorylated tau Ser214 specifically. In vivo transfection of sgk1 also phosphorylated tau Ser214 in HEK293T cells and hippocampal neurons. Further, sgk1 transfection significantly increased the number of primary neurites and shortened the length of the total process in cultured hippocampal neurons. These effects were antagonized by the cotransfection of the tauS214A mutant plasmid. Dexamethasone, a synthetic glucocorticoid, mimics the effect of sgk1 overexpression. Together, these results suggest that SGK1 enhances neurite formation through MT depolymerization by a direct action of SGK1 and by the SGK1 phosphorylation of tau.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1128/mcb.01017-06

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • SGK1 contributes to Tau hyperphosphorylation and microtubule depolymerization.

    “thus contributing to Tau hyperphosphorylation and microtubule depolymerization [18].”

    From Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons (2026) · cites this paper as [18]

    The Results (page not provided) show that SGK1 phosphorylates tau at Ser214 and promotes microtubule depolymerization. They do not establish tau hyperphosphorylation: the paper reports that the other tau phosphorylation sites tested remained unchanged. The Discussion (page not provided) also says SGK1 phosphorylation of tau is probably not related to Alzheimer's disease pathogenesis. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 61

  1. [3]Avila, J., J. Dominguez, and J. Diaz-Nido. 1994. Regulation of microtubule dynamics by microtubule-associated protein expression and phosphorylation during neuronal development. Int. J. Dev. Biol. 38:13-25. [PubMed] [Google Scholar]
  2. [4]Belmont, L. D., and T. J. Mitchison. 1996. Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules. Cell 84:623-631. [DOI] [PubMed] [Google Scholar]
  3. [5]Brummelkamp, T. R., R. Bernards, and R. Agami. 2002. A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550-553. [DOI] [PubMed] [Google Scholar]
  4. [6]Buse, P., S. H. Tran, E. Luther, P. T. Phu, G. W. Aponte, and G. L. Firestone. 1999. Cell cycle and hormonal control of nuclear-cytoplasmic localization of the serum- and glucocorticoid-inducible protein kinase, Sgk, in mammary tumor cells. A novel convergence point of anti-proliferative and proliferative cell signaling pathways. J. Biol. Chem. 274:7253-7263. [DOI] [PubMed] [Google Scholar]
  5. [7]Caceres, A., S. Potrebic, and K. S. Kosik. 1991. The effect of tau antisense oligonucleotides on neurite formation of cultured cerebellar macroneurons. J. Neurosci. 11:1515-1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. [8]Cassimeris, L. 1993. Regulation of microtubule dynamic instability. Cell Motil. Cytoskelet. 26:275-281. [DOI] [PubMed] [Google Scholar]
  7. [9]Cassimeris, L., and C. Spittle. 2001. Regulation of microtubule-associated proteins. Int. Rev. Cytol. 210:163-226. [DOI] [PubMed] [Google Scholar]
  8. [10]Chun, J., T. Kwon, E. J. Lee, C. H. Kim, Y. S. Han, S. K. Hong, S. Hyun, and S. S. Kang. 2004. 14-3-3 Protein mediates phosphorylation of microtubule-associated protein tau by serum- and glucocorticoid-induced protein kinase 1. Mol. Cells 18:360-368. [PubMed] [Google Scholar]
  9. [11]David, S., S. L. Stegenga, P. Hu, G. Xiong, E. Kerr, K. B. Becker, S. Venkatapathy, J. A. Warrington, and R. G. Kalb. 2005. Expression of serum- and glucocorticoid-inducible kinase is regulated in an experience-dependent manner and can cause dendrite growth. J. Neurosci. 25:7048-7053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. [12]Dent, E. W., and F. B. Gertler. 2003. Cytoskeletal dynamics and transport in growth cone motility and axon guidance. Neuron 40:209-227. [DOI] [PubMed] [Google Scholar]
  11. [13]Desai, A., S. Verma, T. J. Mitchison, and C. E. Walczak. 1999. Kin I kinesins are microtubule-destabilizing enzymes. Cell 96:69-78. [DOI] [PubMed] [Google Scholar]
  12. [14]de Silva, R., and M. Farrer. 2002. Tau neurotoxicity without the lesions: a fly challenges a tangled web. Trends Neurosci. 25:327-329. [DOI] [PubMed] [Google Scholar]
  13. [15]Dijkhuizen, P. A., and A. Ghosh. 2005. BDNF regulates primary dendrite formation in cortical neurons via the PI3-kinase and MAP kinase signaling pathways. J. Neurobiol. 62:278-288. [DOI] [PubMed] [Google Scholar]
  14. [16]Firestone, G. L., J. R. Giampaolo, and B. A. O'Keeffe. 2003. Stimulus-dependent regulation of serum and glucocorticoid inducible protein kinase (SGK) transcription, subcellular localization and enzymatic activity. Cell. Physiol. Biochem. 13:1-12. [DOI] [PubMed] [Google Scholar]
  15. [17]Gao, P. P., Y. Yue, D. P. Cerretti, C. Dreyfus, and R. Zhou. 1999. Ephrin-dependent growth and pruning of hippocampal axons. Proc. Natl. Acad. Sci. USA 96:4073-4077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. [18]Goedert, M., R. A. Crowther, and C. C. Garner. 1991. Molecular characterization of microtubule-associated proteins tau and MAP2. Trends Neurosci. 14:193-199. [DOI] [PubMed] [Google Scholar]
  17. [19]Goold, R. G., R. Owen, and P. R. Gordon-Weeks. 1999. Glycogen synthase kinase 3β phosphorylation of microtubule-associated protein 1B regulates the stability of microtubules in growth cones. J. Cell Sci. 112:3373-3384. [DOI] [PubMed] [Google Scholar]
  18. [20]Gustke, N., B. Trinczek, J. Biernat, E. M. Mandelkow, and E. Mandelkow. 1994. Domains of tau protein and interactions with microtubules. Biochemistry 33:9511-9522. [DOI] [PubMed] [Google Scholar]
  19. [21]Hartman, J. J., and R. D. Vale. 1999. Microtubule disassembly by ATP-dependent oligomerization of the AAA enzyme katanin. Science 286:782-785. [DOI] [PubMed] [Google Scholar]
  20. [22]Heald, R., and E. Nogales. 2002. Microtubule dynamics. J. Cell Sci. 115:3-4. [DOI] [PubMed] [Google Scholar]
  21. [23]Hill, C. M., D. S. Libich, and G. Harauz. 2005. Assembly of tubulin by classic myelin basic protein isoforms and regulation by post-translational modification. Biochemistry 44:16672-16683. [DOI] [PubMed] [Google Scholar]
  22. [24]Horwitz, S. B. 1994. Taxol (paclitaxel): mechanisms of action. Ann. Oncol. 5(Suppl 6):S3-S6. [PubMed] [Google Scholar]
  23. [25]Hung, L. Y., H. L. Chen, C. W. Chang, B. R. Li, and T. K. Tang. 2004. Identification of a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and inhibits microtubule assembly. Mol. Biol. Cell 15:2697-2706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. [26]Illenberger, S., Q. Zheng-Fischhofer, U. Preuss, K. Stamer, K. Baumann, B. Trinczek, J. Biernat, R. Godemann, E. M. Mandelkow, and E. Mandelkow. 1998. The endogenous and cell cycle-dependent phosphorylation of tau protein in living cells: implications for Alzheimer's disease. Mol. Biol. Cell 9:1495-1512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. [27]Inoue, S., and E. D. Salmon. 1995. Force generation by microtubule assembly/disassembly in mitosis and related movements. Mol. Biol. Cell 6:1619-1640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. [29]Jourdain, L., P. Curmi, A. Sobel, D. Pantaloni, and M. F. Carlier. 1997. Stathmin: a tubulin-sequestering protein which forms a ternary T2S complex with two tubulin molecules. Biochemistry 36:10817-10821. [DOI] [PubMed] [Google Scholar]
  27. [30]Kobayashi, T., and P. Cohen. 1999. Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. Biochem. J. 339:319-328. [PMC free article] [PubMed] [Google Scholar]
  28. [31]Ksiezak-Reding, H., H. K. Pyo, B. Feinstein, and G. M. Pasinetti. 2003. Akt/PKB kinase phosphorylates separately Thr212 and Ser214 of tau protein in vitro. Biochim. Biophys. Acta 1639:159-168. [DOI] [PubMed] [Google Scholar]
  29. [32]Lee, C. T., S. W. Tyan, Y. L. Ma, M. C. Tsai, Y. C. Yang, and E. H. Lee. 2006. Serum- and glucocorticoid-inducible kinase (SGK) is a target of the MAPK/ERK signaling pathway that mediates memory formation in rats. Eur. J. Neurosci. 23:1311-1320. [DOI] [PubMed] [Google Scholar]
  30. [33]Lee, E., E. S. Lein, and G. L. Firestone. 2001. Tissue-specific expression of the transcriptionally regulated serum and glucocorticoid-inducible protein kinase (Sgk) during mouse embryogenesis. Mech. Dev. 103:177-181. [DOI] [PubMed] [Google Scholar]
  31. [34]Lee, E. H., W. L. Hsu, Y. L. Ma, P. J. Lee, and C. C. Chao. 2003. Enrichment enhances the expression of sgk, a glucocorticoid-induced gene, and facilitates spatial learning through glutamate AMPA receptor mediation. Eur. J. Neurosci. 18:2842-2852. [DOI] [PubMed] [Google Scholar]
  32. [35]Lee, G., and S. L. Rook. 1992. Expression of tau protein in non-neuronal cells: microtubule binding and stabilization. J. Cell Sci. 102:227-237. [DOI] [PubMed] [Google Scholar]
  33. [36]Liedtke, W., E. E. Leman, R. E. Fyffe, C. S. Raine, and U. K. Schubart. 2002. Stathmin-deficient mice develop an age-dependent axonopathy of the central and peripheral nervous systems. Am. J. Pathol. 160:469-480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. [37]Lim, A. C., S. Y. Tiu, Q. Li, and R. Z. Qi. 2004. Direct regulation of microtubule dynamics by protein kinase CK2. J. Biol. Chem. 279:4433-4439. [DOI] [PubMed] [Google Scholar]
  35. [38]Lu, R., H. Wang, Z. Liang, L. Ku, T. O'Donnell, W. Li, S. T. Warren, and Y. Feng. 2004. The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development. Proc. Natl. Acad. Sci. USA 101:15201-15206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. [39]Ma, Y. L., M. C. Tsai, W. L. Hsu, and E. H. Lee. 2006. SGK protein kinase facilitates the expression of long-term potentiation in hippocampal neurons. Learn. Mem. 13:114-118. [DOI] [PubMed] [Google Scholar]
  37. [40]Maiato, H., P. Sampaio, and C. E. Sunkel. 2004. Microtubule-associated proteins and their essential roles during mitosis. Int. Rev. Cytol. 241:53-153. [DOI] [PubMed] [Google Scholar]
  38. [41]Maiyar, A. C., M. L. Leong, and G. L. Firestone. 2003. Importin-alpha mediates the regulated nuclear targeting of serum- and glucocorticoid-inducible protein kinase (Sgk) by recognition of a nuclear localization signal in the kinase central domain. Mol. Biol. Cell 14:1221-1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. [42]Markus, A., J. Zhong, and W. D. Snider. 2002. Raf and Akt mediate distinct aspects of sensory axon growth. Neuron 35:65-76. [DOI] [PubMed] [Google Scholar]
  40. [43]McEwen, B. S. 2005. Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54:20-23. [DOI] [PubMed] [Google Scholar]
  41. [44]McNally, F. J., and R. D. Vale. 1993. Identification of katanin, an ATPase that severs and disassembles stable microtubules. Cell 75:419-429. [DOI] [PubMed] [Google Scholar]
  42. [45]Mershin, A., E. Pavlopoulos, O. Fitch, B. C. Braden, D. V. Nanopoulos, and E. M. Skoulakis. 2004. Learning and memory deficits upon TAU accumulation in Drosophila mushroom body neurons. Learn. Mem. 11:277-287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. [46]Mizuno, H., and E. Nishida. 2001. The ERK MAP kinase pathway mediates induction of SGK (serum- and glucocorticoid-inducible kinase) by growth factors. Genes Cells 6:261-268. [DOI] [PubMed] [Google Scholar]
  44. [47]Nakayama, T., and T. Sawada. 2002. Involvement of microtubule integrity in memory impairment caused by colchicine. Pharmacol. Biochem. Behav. 71:119-138. [DOI] [PubMed] [Google Scholar]
  45. [48]Park, J., M. L. Leong, P. Buse, A. C. Maiyar, G. L. Firestone, and B. A. Hemmings. 1999. Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. EMBO J. 18:3024-3033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. [49]Riederer, B. M., V. Pellier, B. Antonsson, G. Di Paolo, S. A. Stimpson, R. Lutjens, S. Catsicas, and G. Grenningloh. 1997. Regulation of microtubule dynamics by the neuronal growth-associated protein SCG10. Proc. Natl. Acad. Sci. USA 94:741-745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. [50]Rochlin, M. W., K. M. Wickline, and P. C. Bridgman. 1996. Microtubule stability decreases axon elongation but not axoplasm production. J. Neurosci. 16:3236-3246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. [51]Roll-Mecak, A., and R. D. Vale. 2005. The Drosophila homologue of the hereditary spastic paraplegia protein, spastin, severs and disassembles microtubules. Curr. Biol. 15:650-655. [DOI] [PubMed] [Google Scholar]
  49. [52]Sapolsky, R. M., H. Uno, C. S. Rebert, and C. E. Finch. 1990. Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J. Neurosci. 10:2897-2902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. [53]Schneider, A., J. Biernat, M. von Bergen, E. Mandelkow, and E. M. Mandelkow. 1999. Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry 38:3549-3558. [DOI] [PubMed] [Google Scholar]
  51. [54]Stoothoff, W. H., and G. V. Johnson. 2005. Tau phosphorylation: physiological and pathological consequences. Biochim. Biophys. Acta 1739:280-297. [DOI] [PubMed] [Google Scholar]
  52. [55]Trotta, N., G. Orso, M. G. Rossetto, A. Daga, and K. Broadie. 2004. The hereditary spastic paraplegia gene, spastin, regulates microtubule stability to modulate synaptic structure and function. Curr. Biol. 14:1135-1147. [DOI] [PubMed] [Google Scholar]
  53. [56]Tsai, K. J., S. K. Chen, Y. L. Ma, W. L. Hsu, and E. H. Lee. 2002. sgk, a primary glucocorticoid-induced gene, facilitates memory consolidation of spatial learning in rats. Proc. Natl. Acad. Sci. USA 99:3990-3995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. [57]Webster, M. K., L. Goya, Y. Ge, A. C. Maiyar, and G. L. Firestone. 1993. Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. Mol. Cell. Biol. 13:2031-2040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. [58]Wheal, H. V., Y. Chen, J. Mitchell, M. Schachner, W. Maerz, H. Wieland, D. Van Rossum, and J. Kirsch. 1998. Molecular mechanisms that underlie structural and functional changes at the postsynaptic membrane during synaptic plasticity. Prog. Neurobiol. 55:611-640. [DOI] [PubMed] [Google Scholar]
  56. [59]Wu, W., S. Chaudhuri, D. R. Brickley, D. Pang, T. Karrison, and S. D. Conzen. 2004. Microarray analysis reveals glucocorticoid-regulated survival genes that are associated with inhibition of apoptosis in breast epithelial cells. Cancer Res. 64:1757-1764. [DOI] [PubMed] [Google Scholar]
  57. [60]Yang, Y. C., Y. L. Ma, S. K. Chen, C. W. Wang, and E. H. Lee. 2003. Focal adhesion kinase is required, but not sufficient, for the induction of long-term potentiation in dentate gyrus neurons in vivo. J. Neurosci. 23:4072-4080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. [61]Yoshimura, T., Y. Kawano, N. Arimura, S. Kawabata, A. Kikuchi, and K. Kaibuchi. 2005. GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120:137-149. [DOI] [PubMed] [Google Scholar]
  59. [62]Yu, W., J. M. Solowska, L. Qiang, A. Karabay, D. Baird, and P. W. Baas. 2005. Regulation of microtubule severing by katanin subunits during neuronal development. J. Neurosci. 25:5573-5583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. [63]Zheng-Fischhofer, Q., J. Biernat, E. M. Mandelkow, S. Illenberger, R. Godemann, and E. Mandelkow. 1998. Sequential phosphorylation of tau by glycogen synthase kinase-3β and protein kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of antibody AT100 and requires a paired-helical-filament-like conformation. Eur. J. Biochem. 252:542-552. [DOI] [PubMed] [Google Scholar]
  61. [64]Zhou, F. Q., J. Zhou, S. Dedhar, Y. H. Wu, and W. D. Snider. 2004. NGF-induced axon growth is mediated by localized inactivation of GSK-3β and functions of the microtubule plus end binding protein APC. Neuron 42:897-912. [DOI] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Authors
Yang, Y. C., Lin, C. H., & Lee, E. H. Y.
Affiliations
  • Institute of Biomedical Sciences, Academia Sinica (TW)
  • National Defense Medical Center (TW)
Corresponding author
Lee, Eminy H. Y.
ORCID
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
2006-11
Volume
26
Issue
22
Pages
8357-8370
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
DOI
10.1128/mcb.01017-06
PMC
PMC1636775
OpenAlex
W2126776792
Cited by
59
References
4
Citations by year
2026: 4 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 1 · 2017: 6 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 2
FWCI
2.66
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Council
  • Academia Sinica
  • Institute of Biomedical Sciences, Academia Sinica
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
SGK1, serum- and glucocorticoid-inducible kinase 1, neurite formation, microtubule depolymerization, tau phosphorylation, hippocampal neurons, dendritic growth, dexamethasone, glucocorticoids, microtubule assembly
MeSH terms
Serum-Glucocorticoid Regulated Kinases, Animals, Cells, Cultured, Female, Hippocampus, Microtubules, Neurons, Phosphorylation, Serine, Transfection, Neurites, tau Proteins, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review