PMID- 19762425
OWN - NLM
STAT- MEDLINE
DCOM- 20091013
LR  - 20211020
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 136
IP  - 20
DP  - 2009 Oct
TI  - Akt-dependent Pp2a activity is required for epidermal barrier formation during 
      late embryonic development.
PG  - 3423-31
LID - 10.1242/dev.037010 [doi]
AB  - Acquisition of epidermal barrier function occurs late in mouse gestation. Several 
      days before birth a wave of barrier acquisition sweeps across murine fetal skin, 
      converging on dorsal and ventral midlines. We investigated the molecular pathways 
      active during epidermal barrier formation. Akt signaling increased as the barrier 
      wave crossed epidermis and Jun was transiently dephosphorylated. Inhibitor 
      experiments on embryonic explants showed that the dephosphorylation of Jun was 
      dependent on both Akt and protein phosphatase 2A (Pp2a). Inhibition of Pp2a and 
      Akt signaling also caused defects in epidermal barrier formation. These data are 
      compatible with a model for developmental barrier acquisition mediated by Pp2a 
      regulation of Jun dephosphorylation, downstream of Akt signaling. Support for 
      this model was provided by siRNA-mediated knockdown of Ppp2r2a (Pr55alpha or 
      B55alpha), a regulatory subunit of Pp2a expressed in an Akt-dependent manner in 
      epidermis during barrier formation. Ppp2r2a reduction caused significant increase 
      in Jun phosphorylation and interfered with the acquisition of barrier function, 
      with barrier acquisition being restored by inhibition of Jun phosphorylation. Our 
      data provide strong evidence that Ppp2r2a is a regulatory subunit of Pp2a that 
      targets this phosphatase to Jun, and that Pp2a action is necessary for barrier 
      formation. We therefore describe a novel Akt-dependent Pp2a activity that acts at 
      least partly through Jun to affect initial barrier formation during late 
      embryonic epidermal development.
FAU - O'Shaughnessy, Ryan F L
AU  - O'Shaughnessy RF
AD  - Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and 
      the London School of Medicine and Dentistry, London, UK. 
      r.oshaughnessy@ich.ucl.ac.uk
FAU - Welti, Jonathan C
AU  - Welti JC
FAU - Sully, Katherine
AU  - Sully K
FAU - Byrne, Carolyn
AU  - Byrne C
LA  - eng
GR  - C5314/A6695/Cancer Research UK/United Kingdom
GR  - Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090917
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Epidermal Cells
MH  - Epidermis/*embryology/*enzymology
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Keratinocytes/enzymology
MH  - Mice
MH  - Phosphorylation
MH  - Protein Phosphatase 2/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - *Signal Transduction
MH  - Tissue Culture Techniques
PMC - PMC2752394
EDAT- 2009/09/19 06:00
MHDA- 2009/10/14 06:00
PMCR- 2010/04/15
CRDT- 2009/09/19 06:00
PHST- 2009/09/19 06:00 [entrez]
PHST- 2009/09/19 06:00 [pubmed]
PHST- 2009/10/14 06:00 [medline]
PHST- 2010/04/15 00:00 [pmc-release]
AID - dev.037010 [pii]
AID - 3423 [pii]
AID - 10.1242/dev.037010 [doi]
PST - ppublish
SO  - Development. 2009 Oct;136(20):3423-31. doi: 10.1242/dev.037010. Epub 2009 Sep 17.