Published 15 August 2005. doi:10.1083/jcb.200504131
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 4, 559-570
Sgk3 links growth factor signaling to maintenance of progenitor cells in the hair follicle
Laura Alonso1,
Hitoshi Okada2,
Hilda Amalia Pasolli1,
Andrew Wakeham2,
Annick Itie You-Ten2,
Tak W. Mak2,3,4, and
Elaine Fuchs1
1 Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021
2 The Campbell Family Institute for Breast Cancer Research/Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada
3 Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada
4 Department of Immunology, University of Toronto, Toronto, Ontario M5G 2C1, Canada
Correspondence to Elaine Fuchs: fuchslb{at}rockefeller.edu; or Tak W. Mak: tmak{at}uhnresearch.ca
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.
L. Alonso and H. Okada contributed equally to this work.
Abbreviations used in this paper: DP, dermal papilla; ERK, extracellular regulated kinase; ES, embryonic stem; IGF, insulin-like growth factor; IRS, inner root sheath; KO, knockout; MEK, MAPK/ERK kinase; ORS, outer root sheath; P, postnatal day; PGK, phosphoglycerate kinase; Phox, phagocyte oxidase; PI3K, phosphatidylinositol 3 kinase; Pten, phosphatase and tensin homologue on chromosome 10; RIPA, radioimmunoprecipitation assay; Sgk, serum and glucocorticoid responsive kinase; Tcf, T-cell factor; TOPgal, Tcf optimal promoter driving ß-galactosidase; WT, wild type.
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