Sgk3 links growth factor signaling to maintenance of progenitor cells in the hair follicle.
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.
Alonso
Laura
L
Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Okada
Hitoshi
H
Pasolli
Hilda Amalia
HA
Wakeham
Andrew
A
You-Ten
Annick Itie
AI
Mak
Tak W
TW
Fuchs
Elaine
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005298:Fertility / Q000187:drug effects; D018390:Gene Targeting; D018859:Hair Follicle / Q000002:abnormalities / Q000166:cytology* / Q000201:enzymology* / Q000648:ultrastructure; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism*; D011995:Recombination, Genetic / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D000099184:Serum-Glucocorticoid Regulated Kinases
D001973:Bromodeoxyuridine; D004247:DNA; D007334:Insulin-Like Growth Factor I; D036341:Intercellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C523602:Sgk3 protein, mouse; D000099184:Serum-Glucocorticoid Regulated Kinases