Gas6 inhibits apoptosis in vascular smooth muscle: role of Axl kinase and Akt

Journal of Molecular and Cellular Cardiology
M G MelaragnoB C Berk

Abstract

Axl is a receptor tyrosine kinase originally identified as a transforming gene product in human myeloid leukemia cells. Previously, we showed that Axl expression correlated with neointima formation in balloon-injured rat carotid, and that Axl expression was highly regulated by angiotensin II. In the present study we tested the mechanisms by which Axl regulates vascular smooth muscle cell (VSMC) growth focusing on its ability to inhibit apoptosis. Treatment of cultured rat aortic VSMC for 24 h with 0% serum resulted in 19.8 +/- 1.4% apoptotic cells. Treatment of VSMC with 100 ng/ml Gas6 (the putative ligand for Axl) decreased apoptosis to 8.9 +/- 0.7% (P = 0.002, N = 17) as compared to a decrease with 10% serum to 3.0 +/- 0.2% (P = 0.001, N = 17). The ability of Gas6 to prevent apoptosis required both Gas6 binding to Axl and Axl kinase activity since treatment with a soluble, competitive Axl extracellular domain protein or transfection of a kinase inactive mutant (Axl-K567R) completely prevented the anti-apoptotic effect. Prevention of apoptosis by Gas6-Axl required activation of phosphatidyl inositol 3-kinase (PI3K) as shown by treatment with LY294002 or transfection of an Axl deletion mutant that does not bind PI3K (Axl- trian...Continue Reading

Citations

Jan 29, 2013·Targeted Oncology·Hiba el SayadiJean-Yves Blay
May 9, 2014·American Journal of Respiratory Cell and Molecular Biology·Takehiko ShibataCory M Hogaboam
Apr 19, 2008·Nature Reviews. Immunology·Greg Lemke, Carla V Rothlin
Nov 6, 2010·Der Pathologe·J D StrehlK Amann
Apr 30, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kathleen BoehmeStefan O Mueller
Aug 22, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Iris J LeePhilip L Cohen
Apr 29, 2015·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Ozlem Bingol OzakpinarFikriye Uras
Dec 5, 2014·The American Journal of the Medical Sciences·Yu-Wei LiuCheng-Yun Liu
Oct 27, 2006·The FEBS Journal·Sassan Hafizi, Björn Dahlbäck
Apr 24, 2009·Kidney International·Thilo KruegerJürgen Floege
Dec 10, 2009·Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association·Hiroyuki OkaNoriko Yoshimura
Dec 21, 2013·Journal of Thrombosis and Haemostasis : JTH·S LauranceM D Blostein
Jul 21, 2010·Vascular Pharmacology·E M Smolock, V A Korshunov
Oct 21, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yanyan LiYongfu Zhao
Dec 23, 2011·Clinical Science·Vyacheslav A Korshunov
Dec 10, 2014·Metabolic Brain Disease·Rui JiQingxian Lu
May 5, 2011·Molecular and Cellular Endocrinology·Angela PierceMargaret E Wierman
Jan 17, 2015·Annual Review of Immunology·Carla V RothlinSourav Ghosh
Apr 28, 2012·The American Journal of Pathology·Janice Gerloff, Vyacheslav A Korshunov
Dec 20, 2014·Annals of the American Thoracic Society·Takehiko Shibata, Cory M Hogaboam
Mar 10, 2016·Journal of Clinical Pathology·Matthew BrownDavid J Pinato
Nov 2, 2016·International Journal of Molecular Sciences·Mattia BellanPier Paolo Sainaghi
Nov 28, 2017·Clinical Epigenetics·Lu GaoCarrie V Breton
Feb 2, 2018·Molecular Cancer·Guiling WuYang Yang
Apr 22, 2006·Circulation Research·Vyacheslav A KorshunovBradford C Berk
Jan 27, 2007·Circulation Research·Georgina D M CollettAnn E Canfield
Oct 10, 2007·Hypertension·Vyacheslav A KorshunovBradford C Berk
Aug 31, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Thilo KrügerRalf Westenfeld
Feb 23, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Megan E CavetBradford C Berk
Mar 22, 2016·Endocrinology and Metabolism·Jaechan Leem, In Kyu Lee
May 23, 2008·Clinical Journal of the American Society of Nephrology : CJASN·John Danziger
Jan 9, 2015·Nature Reviews. Cancer·Douglas K GrahamH Shelton Earp

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