Work

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

Year: 2001

Type: article

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.

Source: Molecular and Cellular Biology

DOI: 10.1128/mcb.21.11.3671-3683.2001

Authors: John M. Schmitt, Philip J. S. Stork

Institutions: Oregon Health & Science University, Vollum Institute

Language: English

Topic: Protein Kinase Regulation and GTPase Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: Promotion and Mutual Aid Corporation for Private Schools of Japan