The critical roles of serum/glucocorticoid-regulated kinase 3 (SGK3) in the hair follicle morphogenesis and homeostasis: the allelic difference provides novel insights into hair follicle biology.
Mutation in the serum/glucocorticoid regulated kinase 3 (Sgk3, also known as Sgkl or Cisk) gene causes both defective hair follicle development and altered hair cycle in mice. We examined Sgk3-mutant YPC mice (YPC-Sgk3(ypc)/Sgk3(ypc)) and found expression of SGK3 protein with altered function. In the hair follicles of YPC mice, the aberrant differentiation and poor proliferation of hair matrix keratinocytes during the period of postnatal hair follicle development resulted in a complete lack of hair medulla and weak hair. Surprisingly, the length of postnatal hair follicle development and anagen term was shown to be dramatically shortened. Also, phosphorylation of GSK3beta at Ser9 and the nuclear accumulation of beta-catenin were reduced in the developing YPC hair follicle, suggesting that phosphorylation of GSK3beta and WNT-beta-catenin pathway takes part in the SGK3-dependent regulation of hair follicle development. Moreover, the above-mentioned features, especially the hair-cycling pattern, differ from those in other Sgk3-null mutant strains, suggesting that the various patterns of dysfunction in the SGK3 protein may result in phenotypic variation. Our results indicate that SGK3 is a very important and characteristic molecule that plays a critical role in both hair follicle morphogenesis and hair cycling.
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan. aa37158@mail.ecc.u-tokyo.ac.jp
Taro
T
Okada
Yoshiyuki
Y
Ishii
Kentaro
K
Masujin
Akira
A
Yasoshima
Junichiro
J
Matsuda
Atsuo
A
Ogura
Hiroyuki
H
Nakayama
Tetsuo
T
Kunieda
Kunio
K
Doi
D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D018859:Hair Follicle / Q000201:enzymology / Q000254:growth & development* / Q000648:ultrastructure; D006706:Homeostasis; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D009024:Morphogenesis; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012694:Serine / Q000378:metabolism; D051153:Wnt Proteins / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012694:Serine; D051153:Wnt Proteins; D051176:beta Catenin; D000099184:Serum-Glucocorticoid Regulated Kinases