Cyclic AMP-mediated inhibition of cell growth requires the small G protein Rap1

Molecular and Cellular Biology
J M Schmitt, P J Stork

Abstract

In many normal and transformed cell types, the intracellular second messenger cyclic AMP (cAMP) blocks the effects of growth factors and serum on mitogenesis, proliferation, and cell cycle progression. cAMP exerts these growth-inhibitory effects via inhibition of the mitogen-activated protein (MAP) kinase cascade. Here, using Hek293 and NIH 3T3 cells, we show that cAMP's inhibition of the MAP kinase cascade is mediated by the small G protein Rap1. Activation of Rap1 by cAMP induces the association of Rap1 with Raf-1 and limits Ras-dependent activation of ERK. In NIH 3T3 cells, Rap1 is required not only for cAMP's inhibition of ERK activation but for inhibition of cell proliferation and mitogenesis as well.

References

Jan 1, 1975·Annual Review of Biochemistry·I H PastanW B Anderson
Jan 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·P G PolakisF McCormick
Jan 15, 1991·Biochemical and Biophysical Research Communications·M J CampaE G Lapetina
Aug 11, 1988·Nucleic Acids Research·V PizonA Tavitian
Aug 17, 1995·Nature·J Downward
Jun 1, 1995·Endocrine Reviews·N DhanasekaranG L Johnson
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·L M GravesE G Krebs
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·B R SevetsonJ C Lawrence
Nov 12, 1993·Science·S J Cook, F McCormick
May 5, 1995·The Journal of Biological Chemistry·D L AltschulerE G Lapetina
Jun 23, 1995·The Journal of Biological Chemistry·M H Cobb, E J Goldsmith
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·W J KochR J Lefkowitz
Nov 1, 1993·Molecular and Cellular Biochemistry·N G Ahn
Oct 1, 1994·Molecular and Cellular Biology·S HäfnerW Kolch
Jul 1, 1994·Trends in Biochemical Sciences·J AvruchJ M Kyriakis
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·L Van AelstM Wigler
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J Blenis
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·G PagèsJ Pouysségur
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·R G QiuM Symons
Jan 5, 1996·The Journal of Biological Chemistry·A Kikuchi, L T Williams
Jan 19, 1996·The Journal of Biological Chemistry·T OhtsukaY Takai
Jan 19, 1996·The Journal of Biological Chemistry·H ItoA Tanaka
Aug 23, 1996·The Journal of Biological Chemistry·J N LavoieJ Pouysségur
Oct 1, 1996·Molecular and Cellular Biology·H MischakW Kolch
Dec 1, 1996·Current Biology : CB·S J Taylor, D Shalloway

❮ Previous
Next ❯

Citations

Mar 14, 2002·European Journal of Pharmacology·Toshiki NishioRyuichi Kikkawa
Dec 4, 2001·Biology of the Cell·C Peyssonnaux, A Eychène
Jun 21, 2002·Trends in Cell Biology·Philip J S Stork, John M Schmitt
May 27, 2003·Trends in Biochemical Sciences·Philip J S Stork
May 3, 2005·Nature Reviews. Immunology·Leonidas C Platanias
May 15, 2007·Oncogene·Z G Goldsmith, D N Dhanasekaran
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Xiaojing YeThomas J Carew
Aug 5, 2009·The Journal of Biological Chemistry·Martin M EdreiraDaniel L Altschuler
Jun 23, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer D CohenSerrine S Lau
Apr 14, 2004·Molecular Plant-microbe Interactions : MPMI·Changbin ChenMartin B Dickman
Apr 21, 2010·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·William H Walker
Jan 1, 2004·Molecular and Cellular Biology·Heehyoung LeeEdward Seto
Jul 25, 2009·Blood·Lucia StefaniniWolfgang Bergmeier
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Fernando Ribeiro-NetoDaniel L Altschuler
Dec 10, 2014·Critical Reviews in Biochemistry and Molecular Biology·Inbar Azoulay-AlfaguterAdam Mor
Feb 15, 2012·Connective Tissue Research·Chenyu Huang, Rei Ogawa
Oct 21, 2003·International Journal of Cancer. Journal International Du Cancer·Juan F SantibáñezJorge Martínez
Jul 7, 2015·Laboratory Investigation; a Journal of Technical Methods and Pathology·Minjing ZouYufei Shi
Jul 8, 2009·Journal of Cellular Biochemistry·Evgeny WeinbergMiron Weinreb
Apr 3, 2003·Immunological Reviews·Leonard J Appleman, Vassiliki A Boussiotis
Jun 24, 2006·The International Journal of Biochemistry & Cell Biology·Jing ZhaoAnne Klibanski
Mar 4, 2014·Expert Opinion on Therapeutic Targets·Renu Agarwal, Puneet Agarwal
Oct 20, 2001·Experimental Cell Research·M L EdinR L Juliano
Apr 18, 2008·European Journal of Pharmacology·Reinoud GosensHerman Meurs
Jan 24, 2002·Molecular Cell·John M Schmitt, Philip J S Stork

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.