Cyclic AMP-Mediated Inhibition of Cell Growth Requires the Small G Protein Rap1

Authors

John M. Schmitt, George Fox UniversityFollow
Philip J. S. Stork, Oregon Health & Science University

Document Type

Article

Publication Date

2001

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.

Comments

Originally published in Molecular and Cellular Biology, Vol. 21, No. 11, p. 3671–3683, June 2001.

http://mcb.asm.org/

Recommended Citation

Schmitt, John M. and Stork, Philip J. S., "Cyclic AMP-Mediated Inhibition of Cell Growth Requires the Small G Protein Rap1" (2001). Faculty Publications - Department of Biological & Molecular Science. 52.
https://digitalcommons.georgefox.edu/bio_fac/52