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Updated: Mar 21, 2026

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Published on: November 29, 2016
PDK1 Is a Regulator of Epidermal Differentiation that Activates and Organizes Asymmetric Cell Division
Teruki Dainichi1, Matthew S Hayden2, Sung-Gyoo Park3
1Department of Microbiology & Immunology, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA; Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Abstract:
Asymmetric cell division (ACD) in a perpendicular orientation promotes cell differentiation and organizes the stratified epithelium. However, the upstream cues regulating ACD have not been identified. Here, we report that phosphoinositide-dependent kinase 1 (PDK1) plays a critical role in establishing ACD in the epithelium. Production of phosphatidyl inositol triphosphate (PIP3) is localized to the apical side of basal cells. Asymmetric recruitment of atypical protein kinase C (aPKC) and partitioning defective (PAR) 3 is impaired in PDK1 conditional knockout (CKO) epidermis. PDK1(CKO) keratinocytes do not undergo calcium-induced activation of aPKC or IGF1-induced activation of AKT and fail to differentiate. PDK1(CKO) epidermis shows decreased expression of Notch, a downstream effector of ACD, and restoration of Notch rescues defective expression of differentiation-induced Notch targets in vitro. We therefore propose that PDK1 signaling regulates the basal-to-suprabasal switch in developing epidermis by acting as both an activator and organizer of ACD and the Notch-dependent differentiation program.
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