QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 12 September 2006
doi: 10.1242/jcs.03175

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.03175v1 119/19/4033    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pankow, S. Articles by Werner, S. Search for Related Content PubMed PubMed Citation Articles by Pankow, S. Articles by Werner, S. Social Bookmarking                         What's this?

Regulation of epidermal homeostasis and repair by phosphoinositide 3-kinase

¹ Institute of Cell Biology, Department of Biology, ETH Zurich, CH-8093 Zurich, Switzerland
² Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
³ Molecular Oncology, Merck Research Laboratories, Boston, MA 02115, USA

^* Author for correspondence (e-mail: sabine.werner{at}cell.biol.ethz.ch)

Accepted 11 July 2006

The epidermis undergoes continuous self-renewal to maintain its protective function. Whereas growth factors are known to modulate overall skin homeostasis, the intracellular signaling pathways, which control the delicate balance between proliferation and differentiation in keratinocytes, are largely unknown. Here we show transient upregulation of the phosphoinositide 3-kinase (PI3K) catalytic subunits p110 and p110ß in differentiating keratinocytes in vitro, expression of these subunits in the epidermis of normal and wounded skin, and enhanced Akt phosphorylation in the hyperproliferative wound epidermis. Stimulation of PI3K activity in cultured keratinocytes by stable expression of an inducible, constitutively active PI3K mutant promoted cell proliferation and inhibited terminal differentiation in keratinocyte monocultures and induced the formation of a hyperplastic, disorganized and poorly differentiated epithelium in organotypic skin cultures. Activation of PI3K signaling also caused reorganization of the actin cytoskeleton and induced keratinocyte migration in vitro and in skin organ cultures. The identification of 122 genes, which are differentially expressed after induction of PI3K signaling provides insight into the molecular mechanisms underlying the observed effects of active PI3K on keratinocytes and indicates that hyperproliferation may be achieved at the expense of genome integrity. These results identify PI3K as an important intracellular regulator of epidermal homeostasis and repair.

Key words: Keratinocyte, Organotypic culture, Skin, Wound healing

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				R. E. Mills, K. R. Taylor, K. Podshivalova, D. B. McKay, and J. M. Jameson Defects in Skin {gamma}{delta} T Cell Function Contribute to Delayed Wound Repair in Rapamycin-Treated Mice J. Immunol., September 15, 2008; 181(6): 3974 - 3983. [Abstract] [Full Text] [PDF]

				S. Taboubi, J. Milanini, E. Delamarre, F. Parat, F. Garrouste, G. Pommier, J. Takasaki, J.-C. Hubaud, H. Kovacic, and M. Lehmann G{alpha}(q/11)-coupled P2Y2 nucleotide receptor inhibits human keratinocyte spreading and migration FASEB J, December 1, 2007; 21(14): 4047 - 4058. [Abstract] [Full Text] [PDF]

				R. F. L. O'Shaughnessy, J. C. Welti, J. C. Cooke, A. A. Avilion, B. Monks, M. J. Birnbaum, and C. Byrne AKT-dependent HspB1 (Hsp27) Activity in Epidermal Differentiation J. Biol. Chem., June 8, 2007; 282(23): 17297 - 17305. [Abstract] [Full Text] [PDF]