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PMID: 11340161 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 21 ·No. 11 ·2001-06-00 ·Pages 3671-83

Schmitt JM, Stork PJ

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.

MeSH Terms
3T3 Cells Animals Cell Division Cell Line, Transformed Cyclic AMP/metabolism Humans Mice Mitogen-Activated Protein Kinase 1/antagonists & inhibitors,metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases/antagonists & inhibitors,metabolism Proto-Oncogene Proteins c-raf/metabolism rap1 GTP-Binding Proteins/metabolism ras Proteins/metabolism
Chemicals
Cyclic AMP Proto-Oncogene Proteins c-raf Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases rap1 GTP-Binding Proteins ras Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Schmitt J M
Vollum Institute, Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201, USA.
Stork P J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.11.3671-3683.2001
Published
2001-06-00
Pages
3671-83
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86997
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.21.11.3671-3683.2001 PMC Full Text View journal details
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