Targeted disruption of the protein kinase SGK3/CISK impairs postnatal hair follicle development.
Members of the serum- and glucocorticoid-regulated kinase (SGK) family are important mediators of growth factor and hormone signaling that, like their close relatives in the Akt family, are regulated by lipid products of phosphatidylinositol-3-kinase. SGK3 has been implicated in the control of cell survival and regulation of ion channel activity in cultured cells. To begin to dissect the in vivo functions of SGK3, we generated and characterized Sgk3 null mice. These mice are viable and fertile, and in contrast to mice lacking SGK1 or Akt2, respectively, display normal sodium handling and glucose tolerance. However, although normal at birth, by postpartum day 4 they have begun to display an unexpected defect in hair follicle morphogenesis. The abnormality in hair follicle development is preceded by a defect in proliferation and nuclear accumulation of beta-catenin in hair bulb keratinocytes. Furthermore, in cultured keratinocytes, heterologous expression of SGK3 potently modulates activation of beta-catenin/Lef-1-mediated gene transcription. These data establish a role for SGK3 in normal postnatal hair follicle development, possibly involving effects on beta-catenin/Lef-1-mediated gene transcription.
McCormick
James A
JA
Departments of Medicine and Molecular and Cellular Pharmacology, University of California, San Francisco, CA 94143, USA.
Feng
Yuxi
Y
Dawson
Kevin
K
Behne
Martin J
MJ
Yu
Benjamin
B
Wang
Jian
J
Wyatt
Amanda W
AW
Henke
Guido
G
Grahammer
Florian
F
Mauro
Theodora M
TM
Lang
Florian
F
Pearce
David
D
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D018390:Gene Targeting; D005947:Glucose / Q000378:metabolism; D018859:Hair Follicle / Q000201:enzymology* / Q000254:growth & development* / Q000473:pathology; D006801:Humans; D017874:Immediate-Early Proteins; D015603:Keratinocytes / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D051176:beta Catenin; D000099184:Serum-Glucocorticoid Regulated Kinases
D003598:Cytoskeletal Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D005947:Glucose; D017874:Immediate-Early Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012964:Sodium; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D000099184:Serum-Glucocorticoid Regulated Kinases; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C474033:FoxO3 protein, mouse