Targeted Disruption of the Protein Kinase SGK3/CISK Impairs Postnatal Hair Follicle Development

James A. McCormick*, Yuxi Feng ${dagger}$ , Kevin Dawson*, Martin J. Behne ${ddagger}$ , Benjamin Yu ${ddagger}$ , Jian Wang*, Amanda W. Wyatt ${dagger}$ , Guido Henke ${dagger}$ , Florian Grahammer ${dagger}$ , Theodora M. Mauro ${ddagger}$ , Florian Lang ${dagger}$ , and David Pearce* ${sect}$

^*Departments of Medicine, and Molecular and Cellular Pharmacology, University of California, San Francisco, CA 94143; Department of Physiology, University of Tubingen, Tubingen, Germany; and Department of Dermatology, University of California, San Francisco, CA 94143

Monitoring Editor: Richard Assoian

Members of the serum- andglucocorticoid-regulated kinase family are important mediatorsof growth factor and hormone signaling that, like their closerelatives in the Akt family, are regulated by lipid productsof phosphatidylinositol-3-kinase. SGK3 has been implicated inthe control of cell survival and regulation of ion channel activityin cultured cells. To begin to dissect the in vivo functionsof SGK3, we generated and characterized Sgk3 null mice. Thesemice are viable and fertile, and in contrast to mice lackingSGK1 or Akt2 respectively, display normal sodium handling andglucose tolerance. However, although normal at birth, by postpartumday 4 they have begun to display an unexpected defect in hairfollicle morphogenesis. The abnormality in hair follicle developmentis preceded by a defect in proliferation and nuclear accumulationof ${beta}$ -catenin in hair bulb keratinocytes. Furthermore, in culturedkeratinocytes, heterologous expression of SGK3 potently modulatesactivation of ${beta}$ -catenin/Lef-1-mediated gene transcription. Thesedata establish a role for SGK3 in normal postnatal hair follicledevelopment, possibly involving effects on ${beta}$ -catenin/Lef-1-mediatedgene transcription.

Corresponding author. E-mail: pearced{at}medicine.ucsf.edu