Modulation of total Akt kinase by increased expression of a single isoform: requirement of the sphingosine-1-phosphate receptor, Edg3/S1P3, for the VEGF-dependent expression of Akt3 in primary endothelial cells

Experimental Cell Research
Christina B FieberRobin C Muise-Helmericks

Abstract

Akt kinase is an important downstream effector of VEGF in primary endothelial cells (EC), promoting angiogenesis by increased cellular survival, motility and tubulogenesis. Akt1 is the founding member of a family of serine threonine kinases thought to have overlapping function. We sought to determine if other Akt family members were also regulated by VEGF in EC. We show that treatment of EC with the angiogenic inducers VEGF or sphingosine-1-phosphate (S1P) results in an increased stabilization of Akt3 mRNA, concurrent with a PI3 kinase-dependent, Akt1-independent increase in both the protein and its phosphorylation. Given the similarity of Akt3 regulation by VEGF and S1P, the sensitivity of VEGF stimulation to the Gi-protein uncoupling reagent, pertussis toxin was tested and shows that VEGF stimulation requires Gi-protein signaling. We show that the VEGF stimulates the expression of Edg3/S1P3 (S1P3) and that expression of this Gi-protein-coupled receptor is both sufficient and necessary for the expression of Akt3. Blockade of a single isoform does not overtly affect cellular function, whereas inhibition of both kinases results in an increase in apoptosis and a down-regulation of cyclin D3. These results suggest a model whereby ...Continue Reading

References

Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J Q ChengJ R Testa
Nov 1, 1995·Trends in Biochemical Sciences·J L Bos
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·J Q ChengJ R Testa
Sep 25, 1997·Trends in Biochemical Sciences·B M Marte, J Downward
Oct 29, 1998·The Journal of Biological Chemistry·R C Muise-HelmericksN Rosen
Jan 8, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·N SchiavoneS Capaccioli
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·B H JiangP K Vogt
Mar 4, 2000·The Biochemical Journal·B Vanhaesebroeck, D R Alessi
Mar 18, 2000·The Journal of Biological Chemistry·T KondoT Okazaki
Jul 6, 2000·The Biochemical Journal·S Pyne, N J Pyne
Nov 10, 2000·Biochemical and Biophysical Research Communications·K B SandauB Brüne
Mar 3, 2001·Neoplasia : an International Journal for Oncology Research·Z ZhangR N DuBois
Nov 10, 2001·Trends in Biochemical Sciences·D P Brazil, B A Hemmings
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·T O Chan, P N Tsichlis
Feb 21, 2002·The Biochemical Journal·Elisabetta MeacciPaola Bruni
Apr 23, 2002·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·David MazuraisThierry Calmels
Jun 19, 2002·Biochimica Et Biophysica Acta·Michael J Kluk, Timothy Hla
Jun 19, 2002·Biochimica Et Biophysica Acta·Sandra Siehler, David R Manning
Jun 19, 2002·Biochimica Et Biophysica Acta·Denis EnglishJoe G N Garcia
Jun 29, 2002·Circulation Research·Ichiro Shiojima, Kenneth Walsh
Dec 11, 2002·The Journal of Pathology·Ester W J A AlbrechtHarry van Goor
Jul 10, 2003·Cell Cycle·Jiyong Liang, Joyce M Slingerland
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Junsuke IgarashiThomas Michel
Oct 4, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kim R LavenburgRobin C Muise-Helmericks
Oct 31, 2003·Cancer Cell·George C Prendergast
Dec 10, 2003·Oncogene·Thomas F FrankeChizuru Sugimoto
Jul 10, 2004·Experimental Cell Research·Laura M DeBuskPengnian Charles Lin
Feb 17, 2005·Molecular and Cellular Biology·Rachael M EastonMorris J Birnbaum
Mar 9, 2005·The Journal of Cell Biology·Eijiro YamadaMasatomo Mori

❮ Previous
Next ❯

Citations

Jun 6, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gary L WrightRobin C Muise-Helmericks
Jun 27, 2008·Pharmacological Reviews·Virginia M Miller, Sue P Duckles
Feb 18, 2011·Journal of Cellular and Molecular Medicine·Elisa TramentozziPaola Finotti
Feb 26, 2011·International Journal of Cancer. Journal International Du Cancer·Tiera A LibyRobin C Muise-Helmericks
May 30, 2015·Molecular Biology of the Cell·Monica Hellesøy, James B Lorens
Apr 21, 2010·The Journal of Biological Chemistry·Giuditta IlluzziAlessandro Prinetti
Aug 31, 2011·Stem Cells International·Alexander KlegerThomas Seufferlein
Oct 2, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Daniel G CorumRobin C Muise-Helmericks

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

International Journal of Cancer. Journal International Du Cancer
Tiera A LibyRobin C Muise-Helmericks
FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Kim R LavenburgRobin C Muise-Helmericks
© 2021 Meta ULC. All rights reserved