Inhibition of Rac activation as a mechanism for negative regulation of actin cytoskeletal reorganization and cell motility by cAMP

The Biochemical Journal
Shin-ya NagasawaYoh Takuwa

Abstract

cAMP has been found to play a role in mediating the negative regulation of cell motility, although its underlying molecular mechanism remains poorly understood. By using CHO (Chinese-hamster ovary) cells that express the EP2 subtype of PGE2 (prostaglandin E2) receptors, we provide evidence that an increase in cellular cAMP content leads to inhibition of cellular Rac activity, which serves as a mechanism for this negative regulation. In CHO cells expressing EP2, but not in vector control cells, PGE2 dose-dependently inhibited chemotaxis towards IGF-I (insulin-like growth factor-I), which is a Rac-dependent process, with the maximal 75% inhibition observed at 10(-8) M PGE2. EP2 stimulation failed to inhibit tyrosine phosphorylation either of IGF-I receptor or IRS-1 (insulin receptor substrate-1), or activation of phosphoinositide 3-kinase or Akt in response to IGF-I, but potently and dose-dependently inhibited IGF-I-induced activation of cellular Rac activity and membrane ruffling. However, PGE2 failed to inhibit Val12-Rac-induced membrane ruffling. Similar to the case of CHO cells, PGE2 inhibited PDGF (platelet-derived growth factor)-induced Rac activation and chemotaxis in vascular smooth muscle cells endogenously expressing EP...Continue Reading

References

Apr 16, 1991·Biochimica Et Biophysica Acta·M Stoker, E Gherardi
Feb 9, 1996·Cell·D A Lauffenburger, A F Horwitz
Dec 31, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·K YasunariJ Yoshikawa
Feb 7, 1998·Science·A Hall
Oct 3, 1999·Physiological Reviews·S NarumiyaF Ushikubi
Oct 19, 2001·The Journal of Biological Chemistry·K L O'Connor, A M Mercurio
Jun 24, 2003·Nature Cell Biology·Marjorie MailletFrank Lezoualc'h
Dec 6, 2003·Science·Anne J RidleyAlan Rick Horwitz

❮ Previous
Next ❯

Citations

Jun 16, 2009·Nature Neuroscience·Anna G OrrStephen F Traynelis
May 12, 2012·Prostaglandins & Other Lipid Mediators·David M AronoffPeter Mancuso
Jun 21, 2008·Brain Research·Takayuki NaganoMotohiko Takemura
Aug 22, 2007·Cell Host & Microbe·Jeongmin SongSoman N Abraham
Feb 1, 2008·Biology of Reproduction·Catalin NicolaChandan Chakraborty
Jun 8, 2012·BioFactors·Yoh TakuwaNoriko Takuwa
Oct 5, 2010·Integrative Biology : Quantitative Biosciences From Nano to Macro·Antoine A Khalil, Peter Friedl
Dec 21, 2014·Molecular Cancer Therapeutics·Béatrice DiratFrédéric Bost

❮ 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.