Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts

Biological Chemistry
Stephanie SchwalmA Huwiler

Abstract

Both of the sphingosine kinase (SK) subtypes SK-1 and SK-2 catalyze the production of the bioactive lipid molecule sphingosine 1-phosphate (S1P). However, the subtype-specific cellular functions are largely unknown. In this study, we investigated the cellular function of SK-2 in primary mouse renal mesangial cells (mMC) and embryonic fibroblasts (MEF) from wild-type C57BL/6 or SK-2 knockout (SK2ko) mice. We found that SK2ko cells displayed a significantly higher proliferative and migratory activity when compared to wild-type cells, with concomitant increased cellular activities of the classical extracellular signal regulated kinase (ERK) and PI3K/Akt cascades, and of the small G protein RhoA. Furthermore, we detected an upregulation of SK-1 protein and S1P3 receptor mRNA expression in SK-2ko cells. The MEK inhibitor U0126 and the S1P1/3 receptor antagonist VPC23019 blocked the increased migration of SK-2ko cells. Additionally, S1P3ko mesangial cells showed a reduced proliferative behavior and reduced migration rate upon S1P stimulation, suggesting a crucial involvement of the S1P3 receptor. In summary, our data demonstrate that SK-2 exerts suppressive effects on cell growth and migration in renal mesangial cells and fibroblasts...Continue Reading

References

Jul 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·A HuwilerJ Pfeilschifter
Jul 11, 1998·The Journal of Biological Chemistry·M F FavataJ M Trzaskos
Jun 1, 2000·Biochimica Et Biophysica Acta·A HuwilerK Sandhoff
Feb 24, 2001·Mammalian Genome : Official Journal of the International Mammalian Genome Society·E R LinnellE M Simpson
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Nov 26, 2002·Biochemical and Biophysical Research Communications·Makoto OsadaYukio Ozaki
Dec 18, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Susumu KatsumaGozoh Tsujimoto
Mar 18, 2003·Bioorganic & Medicinal Chemistry Letters·Micheal D GaulKaren Lackey
Jul 2, 2003·The Journal of Biological Chemistry·Hong LiuSarah Spiegel
Sep 5, 2003·The Journal of Biological Chemistry·Nobuaki IgarashiShun-ichi Nakamura
May 5, 2005·Molecular and Cellular Biology·Sravan K GoparajuSarah Spiegel
Mar 21, 2006·Nature·Olivier PertzKlaus M Hahn
Apr 25, 2006·The Journal of Pharmacology and Experimental Therapeutics·Kevin J FrenchCharles D Smith
Dec 16, 2006·Current Pharmaceutical Design·Andrea Huwiler, Josef Pfeilschifter
Feb 22, 2007·The Journal of Biological Chemistry·Nitai C HaitSarah Spiegel
Dec 7, 2007·Breast Cancer Research and Treatment·Eugen RuckhäberleManfred Kaufmann
Aug 12, 2008·Current Drug Targets·Dai ShidaSarah Spiegel
Oct 31, 2008·Kidney International·Sang-Kyung JoMark D Okusa
Jan 12, 2010·The Journal of Pharmacology and Experimental Therapeutics·Kevin J FrenchCharles D Smith
Sep 24, 2010·Endocrinology·James W AntoonBarbara S Beckman
Sep 27, 2012·Rheumatology International·DeAnna A BakerGary S Gilkeson
Aug 14, 2013·FEMS Yeast Research·Cláudia BessaLucília Saraiva
Aug 21, 2013·Nature Reviews. Drug Discovery·Gregory T KunkelSarah Spiegel
Sep 13, 2013·Small GTPases·Kathleen O'Connor, Min Chen

❮ Previous
Next ❯

Citations

May 6, 2016·Frontiers in Pharmacology·Anja SchwiebsHeinfried H Radeke
Mar 12, 2017·International Journal of Molecular Sciences·Louise Tzung-Harn HsiehLiliana Schaefer
Nov 2, 2016·Journal of the American Society of Nephrology : JASN·Amandeep BajwaMark D Okusa
Aug 18, 2017·Journal of Lipid Research·Rajesh K SinghFrederick R Maxfield
Jun 20, 2017·Frontiers in Pharmacology·Ambra VestriElisabetta Meacci
Jan 8, 2021·Journal of Cellular Physiology·Xuehui FanGuozhong Li
Sep 30, 2021·Biological Reviews of the Cambridge Philosophical Society·Mengqiao CuiHongjie Zhang

❮ 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.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.