Journal article
PKC activation differentially increases sFlt1 expression in human vascular endothelium
The FASEB journal, Vol.20(4), pp.A750-A750
03/2006
DOI: 10.1096/fasebj.20.4.A750-b
Abstract
FLT1 gene produces two transcripts from a common transcription start site: full length Flt1 contains 30 spliced exons and encodes a membrane bound VEGF receptor. sFlt1 shares the first 13 exons but utilizes intron 13 poly(A) signal sequences to create a shorter transcript that lacks exon 14 to 30. sFlt1 encodes a circulating soluble variant that serves as a natural antagonist to VEGF. We investigated the effect of protein kinase C (PKC) activation on sFlt1 and Flt1 expression in human umbilical vein endothelial cells (HUVEC). Phorbol myristic acid (PMA) robustly stimulated sFlt1 mRNA expression and this expression preceded the large increase in sFlt1 protein secreted into conditioned culture media. The effect of PMA on sFlt1 mRNA and protein was substantially reduced by GF109203X and by PD98059 indicating that this stimulation was mediated via the activation of PKC and ERK. The effect of PKC activation on steady state sFlt1 and Flt1 mRNA was then measured simultaneously demonstrating that PKC activation differentially increases sFlt1 expression (fold increase in sFlt1 with PMA: 27.2 ± 5.9 vs increase in Flt1: 2 fold ± 0.59). Our data indicates that PKC activation differentially regulates sFlt1 expression in HUVEC, perhaps, by selectively increasing the alternate processing of sFlt1.
Details
- Title: Subtitle
- PKC activation differentially increases sFlt1 expression in human vascular endothelium
- Creators
- Christie P Thomas - University of IowaKang Z Liu - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.20(4), pp.A750-A750
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.4.A750-b
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Obstetrics and Gynecology; Internal Medicine; Nephrology; Stead Family Department of Pediatrics
- Record Identifier
- 9984201121102771
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