Linkki PI-3K ja Gas6 ( K-vitamiiniaineenvaihdunnan) peptidin kesken

http://www.ncbi.nlm.nih.gov/pubmed/18680538

LÄHDE: 

J Thromb Haemost. 2008 Oct;6(10):1804-11. Epub 2008 Aug 1. GAS6-induced signaling in human endothelial cells is mediated by FOXO1a.

Ganopolsky JG, Abid MR, Aird WC, Blostein MD. SourceThe Lady Davis Institute, Sir Mortimer Davis Jewish General Hospital, McGill University, Montreal, QC, Canada.

Abstract,  TIIVISTELMÄ

BACKGROUND, Tausta: 

Growth Arrest Specific gene product 6 (gas6) is a gamma-carboxylated protein that protects endothelial cells against apoptosis. Gas6 has previously been shown to induce phospatidyl-3-inositol-kinase (PI3K)/Akt signaling. Other studies have demonstrated a link between PI3K/Akt signaling and forkhead transcription factors in endothelial cells.

Gas6 geenituote on gammakarboksyloitu proteiini, joka suojaa verisuonen sisäpintaa, endoteelia, apoptoosia vastaan.  Aiemmin on osoitettu, että Gas6 indusoi PI-3K/Akt-signalointi tien. Toiset tutkimukset ovat osoittaneet taas  endoteelin PI-3K/Akt signaloinnilla  ja DNA-haarukan transkriptiotekijöillä olevan yhteistä linkkiä.

OBJECTIVE: Tutkimuksen kohde:

To test the hypothesis that gas6 promotes cell survival via a forkhead-dependent pathway.

Tarkoituksena on testata hypoteesia siiteä, että tämä K-vitamiinia vaativa Gas6 edistää solun elossapysymistä tavalla, joka on riippuvainen DNA-replikaatiohaarukasta. 

RESULTS AND CONCLUSIONS:Tulokset ja yhteenveto.

Treatment of serum-starved human umbilical vein endothelial cells (HUVECs) with gas6 induced time-dependent phosphorylation and nuclear exclusion of FOXO1a.

This effect was suppressed by the PI3K inhibitor wortmannin, demonstrating that FOXO1a phosphorylation is PI3-kinase dependent.

 Transduction of HUVECs with a phosphorylation-resistant form of FOXO1a [triple mutant (TM)-FOXO1a] abrogated the pro-survival effect of gas6 on serum-starved endothelial cells.

Finally, treatment of serum-starved HUVECs with gas6 resulted in a reduction of FOXO1a transcriptional activity and downregulation of the pro-apoptotic gene, p27(kip1).

 Taken together, these findings suggest that gas6 protects endothelial cells from apoptosis by a mechanism that involves PI3K-Akt-dependent inactivation of FOXO1a.