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PMID: 16103225 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Sgk3 links growth factor signaling to maintenance of progenitor cells in the hair follicle.

The Journal of cell biology ·Vol. 170 ·No. 4 ·2005-08-15 ·Pages 559-70

Alonso L, Okada H, Pasolli HA, Wakeham A, You-Ten AI, Mak TW, Fuchs E

Abstract

Tyrosine kinase growth factor receptor signaling influences proliferation, survival, and apoptosis. Hair follicles undergo cycles of proliferation and apoptotic regression, offering an excellent paradigm to study how this transition is governed. Several factors are known to affect the hair cycle, but it remains a mystery whether Akt kinases that are downstream of growth factor signaling impact this equilibrium. We now show that an Akt relative, Sgk (serum and glucocorticoid responsive kinase) 3, plays a critical role in this process. Hair follicles of mice lacking Sgk3 fail to mature normally. Proliferation is reduced, apoptosis is increased, and follicles prematurely regress. Maintenance of the pool of transiently amplifying matrix cells is impaired. Intriguingly, loss of Sgk3 resembles the gain of function of epidermal growth factor signaling. Using cultured primary keratinocytes, we find that Sgk3 functions by negatively regulating phosphatidylinositol 3 kinase signaling. Our results reveal a novel and important function for Sgk3 in controlling life and death in the hair follicle.

MeSH Terms
Animals Apoptosis/drug effects Bromodeoxyuridine Cell Count Cell Differentiation/drug effects Cell Proliferation/drug effects DNA/biosynthesis Fertility/drug effects Gene Targeting Hair Follicle/abnormalities,cytology,enzymology,ultrastructure Insulin-Like Growth Factor I/pharmacology Intercellular Signaling Peptides and Proteins/metabolism Keratinocytes/drug effects,metabolism Mice Morphogenesis/drug effects Protein Serine-Threonine Kinases/deficiency,metabolism Recombination, Genetic/drug effects Regeneration/drug effects S Phase/drug effects Signal Transduction/drug effects Stem Cells/cytology,drug effects
Chemicals
Intercellular Signaling Peptides and Proteins Insulin-Like Growth Factor I DNA Protein Serine-Threonine Kinases Sgk3 protein, mouse Bromodeoxyuridine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Alonso Laura
Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Okada Hitoshi
Pasolli Hilda Amalia
Wakeham Andrew
You-Ten Annick Itie
Mak Tak W
Fuchs Elaine
References (45)
45 references, click to expand
  1. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases.
    Science. 2002 Dec 6;298(5600):1911-2 PMID: 12471242
  2. Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation.
    Cancer Res. 2003 Feb 1;63(3):674-81 PMID: 12566313
  3. Stimulus-dependent regulation of serum and glucocorticoid inducible protein kinase (SGK) transcription, subcellular localization and enzymatic activity.
    Cell Physiol Biochem. 2003;13(1):1-12 PMID: 12649597
  4. The ErbB receptors and their role in cancer progression.
    Exp Cell Res. 2003 Mar 10;284(1):99-110 PMID: 12648469
  5. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2.
    Genes Dev. 2003 Jun 1;17(11):1352-65 PMID: 12782654
  6. PTEN: from pathology to biology.
    Trends Cell Biol. 2003 Sep;13(9):478-83 PMID: 12946627
  7. Capturing and profiling adult hair follicle stem cells.
    Nat Biotechnol. 2004 Apr;22(4):411-7 PMID: 15024388
  8. Targeted disruption of the protein kinase SGK3/CISK impairs postnatal hair follicle development.
    Mol Biol Cell. 2004 Sep;15(9):4278-88 PMID: 15240817
  9. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.
    Cell. 2004 Sep 3;118(5):635-48 PMID: 15339667
  10. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes.
    Nature. 1977 Feb 3;265(5593):421-4 PMID: 299924
  11. Effects of epidermal growth factor on hair growth in the mouse.
    J Endocrinol. 1981 Feb;88(2):293-9 PMID: 6970792
  12. Inhibition of wool growth in merino sheep following administration of mouse epidermal growth factor and a derivative.
    Aust J Biol Sci. 1982;35(2):163-72 PMID: 6982038
  13. Morphological changes in the skin and wool fibres of Merino sheep infused with mouse epidermal growth factor.
    Aust J Biol Sci. 1983;36(4):419-34 PMID: 6362638
  14. Apoptosis in wool follicles during mouse epidermal growth factor (mEGF)-induced catagen regression.
    J Invest Dermatol. 1987 Apr;88(4):455-8 PMID: 3494087
  15. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r).
    Cell. 1993 Oct 8;75(1):59-72 PMID: 8402901
  16. Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-I at physiologic concentrations is an important regulator of hair follicle growth in vitro.
    J Invest Dermatol. 1994 Jun;102(6):857-61 PMID: 8006448
  17. FGF5 as a regulator of the hair growth cycle: evidence from targeted and spontaneous mutations.
    Cell. 1994 Sep 23;78(6):1017-25 PMID: 7923352
  18. Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice.
    Genes Dev. 1994 Nov 15;8(22):2691-703 PMID: 7958926
  19. Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate.
    Genes Dev. 1995 Mar 15;9(6):700-13 PMID: 7537238
  20. Expression of a dominant negative mutant of epidermal growth factor receptor in the epidermis of transgenic mice elicits striking alterations in hair follicle development and skin structure.
    EMBO J. 1995 Nov 1;14(21):5216-23 PMID: 7489711
  21. Keratinocyte growth factor is required for hair development but not for wound healing.
    Genes Dev. 1996 Jan 15;10(2):165-75 PMID: 8566750
  22. Increased vibrissa growth in transgenic mice expressing insulin-like growth factor 1.
    J Invest Dermatol. 1999 Feb;112(2):245-8 PMID: 9989803
  23. 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. 1999 Apr 15;339 ( Pt 2):319-28 PMID: 10191262
  24. Roles for PDGF-A and sonic hedgehog in development of mesenchymal components of the hair follicle.
    Development. 1999 Jun;126(12):2611-21 PMID: 10331973
  25. Enhancement of susceptibility to diverse skin tumor promoters by activation of the insulin-like growth factor-1 receptor in the epidermis of transgenic mice.
    Mol Carcinog. 1999 Jun;25(2):122-31 PMID: 10365914
  26. Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation.
    Development. 1999 Oct;126(20):4557-68 PMID: 10498690
  27. Epithelium-mesenchyme interactions control the activity of peroxisome proliferator-activated receptor beta/delta during hair follicle development.
    Mol Cell Biol. 2005 Mar;25(5):1696-712 PMID: 15713628
  28. Molecular principles of hair follicle induction and morphogenesis.
    Bioessays. 2005 Mar;27(3):247-61 PMID: 15714560
  29. Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase.
    Biochem J. 1999 Nov 15;344 Pt 1:189-97 PMID: 10548550
  30. Cellular survival: a play in three Akts.
    Genes Dev. 1999 Nov 15;13(22):2905-27 PMID: 10579998
  31. Insulin-like growth factor 1 and hair growth.
    Dermatol Online J. 1999 Nov;5(2):1 PMID: 10673454
  32. Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion.
    Cancer Res. 2000 Mar 15;60(6):1561-70 PMID: 10749124
  33. Involvement of follicular stem cells in forming not only the follicle but also the epidermis.
    Cell. 2000 Aug 18;102(4):451-61 PMID: 10966107
  34. Identification of CISK, a new member of the SGK kinase family that promotes IL-3-dependent survival.
    Curr Biol. 2000 Oct 5;10(19):1233-6 PMID: 11050396
  35. Controls of hair follicle cycling.
    Physiol Rev. 2001 Jan;81(1):449-494 PMID: 11152763
  36. Morphogenesis and renewal of hair follicles from adult multipotent stem cells.
    Cell. 2001 Jan 26;104(2):233-45 PMID: 11207364
  37. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages.
    J Invest Dermatol. 2001 Jul;117(1):3-15 PMID: 11442744
  38. Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides.
    J Cell Biol. 2001 Aug 20;154(4):699-705 PMID: 11514587
  39. Activation of the Akt-related cytokine-independent survival kinase requires interaction of its phox domain with endosomal phosphatidylinositol 3-phosphate.
    Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12908-13 PMID: 11606732
  40. Regulation and physiological roles of serum- and glucocorticoid-induced protein kinase isoforms.
    Sci STKE. 2001 Nov 13;2001(108):re17 PMID: 11707620
  41. Fibroblast growth factor signalling in the hair growth cycle: expression of the fibroblast growth factor receptor and ligand genes in the murine hair follicle.
    Dev Dyn. 1996 Apr;205(4):379-86 PMID: 8901049
  42. Overexpression of insulin-like growth factor-1 induces hyperplasia, dermal abnormalities, and spontaneous tumor formation in transgenic mice.
    Oncogene. 1997 Apr 10;14(14):1725-34 PMID: 9135074
  43. Angora mouse mutation: altered hair cycle, follicular dystrophy, phenotypic maintenance of skin grafts, and changes in keratin expression.
    Vet Pathol. 1997 May;34(3):171-9 PMID: 9163872
  44. Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development.
    Am J Pathol. 1997 Jun;150(6):1959-75 PMID: 9176390
  45. Strategies of epithelial repair: modulation of stem cell and transit amplifying cell proliferation.
    J Cell Sci. 1998 Oct;111 ( Pt 19):2867-75 PMID: 9730979
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200504131
Published
2005-08-15
Pages
559-70
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC1283094
Subset
IM
Grants
NIAMS NIH HHS · R01 AR031737 · United States
External Links
PubMed source DOI: 10.1083/jcb.200504131 PMC Full Text View journal details
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