AKT1 provides an essential survival signal required for differentiation and stratification of primary human keratinocytes

The Journal of Biological Chemistry
Barry R ThrashDennis J McCance

Abstract

Keratinocyte differentiation and stratification are complex processes involving multiple signaling pathways, which convert a basal proliferative cell into an inviable rigid squame. Loss of attachment to the basement membrane triggers keratinocyte differentiation, while in other epithelial cells, detachment from the extracellular matrix leads to rapid programmed cell death or anoikis. The potential role of AKT in providing a survival signal necessary for stratification and differentiation of primary human keratinocytes was investigated. AKT activity increased during keratinocyte differentiation and was attributed to the specific activation of AKT1 and AKT2. Targeted reduction of AKT1 expression, but not AKT2, by RNA interference resulted in an abnormal epidermis in organotypic skin cultures with a thin parabasal region and a pronounced but disorganized cornified layer. This abnormal stratification was due to significant cell death in the suprabasal layers and was alleviated by caspase inhibition. Normal expression patterns of both early and late markers of keratinocyte differentiation were also disrupted, producing a poorly developed stratum corneum.

References

Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D J McCanceL A Laimins
Oct 23, 1997·Current Opinion in Cell Biology·S M Frisch, E Ruoslahti
Oct 29, 1998·Biochemical and Biophysical Research Communications·M R Calera, P F Pilch
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·B H JiangP K Vogt
Apr 20, 1999·Biochemical and Biophysical Research Communications·K NakataniR A Roth
Sep 15, 1999·Nature·J A Romashkova, S S Makarov
Dec 2, 1999·Genes & Development·S R DattaM E Greenberg
Jan 14, 2000·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·G P Dotto
Feb 17, 2000·The Journal of Clinical Investigation·C S SeitzP A Khavari
Mar 8, 2000·Experimental Gerontology·A Gandarillas
Oct 5, 2001·Molecular and Cellular Biology·J M ParamioJ L Jorcano
Apr 12, 2002·The Journal of Biological Chemistry·Satoshi KanekoJin Q Cheng
Apr 25, 2002·Nature Reviews. Genetics·Elaine Fuchs, Srikala Raghavan
Aug 17, 2002·The Journal of Biological Chemistry·Koji SayamaKoji Hashimoto
Apr 1, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiro UmedaJunji Takeda
Jan 20, 2004·Genes & Development·Maranke I KosterDennis R Roop
Jan 30, 2004·Proceedings of the National Academy of Sciences of the United States of America·Stéphanie A BackmanTak W Mak
Nov 24, 2004·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Lorenzo AlibardiLeopold Eckhart
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
Jun 21, 2005·The Journal of Biological Chemistry·Judith A MackEdward V Maytin
Jul 23, 2005·The Journal of Biological Chemistry·Enzo CalauttiPaul F Goetinck
Oct 14, 2005·The Journal of Biological Chemistry·Richard C Hresko, Mike Mueckler

❮ Previous
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Citations

Sep 11, 2012·Archives of Dermatological Research·Antonio Peramo, Cynthia L Marcelo
Feb 18, 2009·Apoptosis : an International Journal on Programmed Cell Death·Saskia LippensWim Declercq
Feb 1, 2011·Archives of Biochemistry and Biophysics·Haixia QinWendy B Bollag
Dec 14, 2011·The Pharmacogenomics Journal·S ParmarJ C Stingl
Apr 29, 2008·Tissue Engineering. Part a·Angela L GibsonB Lynn Allen-Hoffmann
Dec 10, 2009·Molecular and Cellular Biology·Aditi MukherjeePeter Rotwein
Nov 9, 2011·Molecular and Cellular Biology·Aditi Mukherjee, Peter Rotwein
Jun 9, 2012·Cells, Tissues, Organs·Carmen ZhangBrian J Aneskievich
Apr 5, 2013·EMBO Molecular Medicine·Daisuke NanbaYann Barrandon
Nov 2, 2011·Seminars in Cell & Developmental Biology·Samantha LinSpiro Getsios
Jun 23, 2015·The Journal of Investigative Dermatology·Minjun YuDonna L Farber
Feb 13, 2008·The Journal of Investigative Dermatology·Eliane J MüllerMaja M Suter
Jun 3, 2011·The Journal of Investigative Dermatology·Teruki YanagiHiroshi Shimizu
May 15, 2008·Biochemical and Biophysical Research Communications·Itamar GorenStefan Frank
Jan 15, 2009·Journal of Cellular Physiology·Peter Rotwein, Elizabeth M Wilson
Apr 30, 2010·The Journal of Investigative Dermatology·Nan-Hyung Kim, Ai-Young Lee
Feb 27, 2010·Biochemical and Biophysical Research Communications·Nagisa KamiokaMotoi Ohba
Sep 13, 2011·The American Journal of Pathology·Sohel M JuloviChristopher John Jackson
Mar 30, 2016·The Journal of Investigative Dermatology·Olufolake AkinduroDaniele Bergamaschi
Dec 21, 2016·Journal of Cellular Physiology·Wei Xie, Jun Zhou
May 31, 2018·Experimental Dermatology·Clare Rogerson, Ryan F L O'Shaughnessy
May 12, 2012·Annals of Dermatology·Ai-Young Lee
Apr 27, 2007·Journal of Cellular Physiology·Lavinia Vittoria LottiCinzia Marchese
Nov 9, 2010·Experimental Dermatology·Nan-Hyung Kim, Ai-Young Lee
Jan 16, 2007·The Journal of Biological Chemistry·Elizabeth M Wilson, Peter Rotwein
Jul 23, 2013·Oncotarget·Ann-Christin CichonDennis J McCance
Jun 7, 2007·The Journal of Biological Chemistry·V'yacheslav Lehen'kyiNatalia Prevarskaya
Apr 19, 2007·The Journal of Biological Chemistry·Ryan F L O'ShaughnessyCarolyn Byrne
Sep 22, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Peter Rotwein

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