| First Author | Dainichi T | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 8 | Pages | 1615-23 |
| PubMed ID | 27184845 | Mgi Jnum | J:269851 |
| Mgi Id | MGI:6274148 | Doi | 10.1016/j.celrep.2016.04.051 |
| Citation | Dainichi T, et al. (2016) PDK1 Is a Regulator of Epidermal Differentiation that Activates and Organizes Asymmetric Cell Division. Cell Rep 15(8):1615-23 |
| abstractText | 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. |
