TY - JOUR
T1 - Cyclic AMP-mediated inhibition of cell growth requires the small G protein Rap1
AU - Schmitt, John M.
AU - Stork, Philip J.S.
PY - 2001/6
Y1 - 2001/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034996666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034996666&partnerID=8YFLogxK
U2 - 10.1128/MCB.21.11.3671-3683.2001
DO - 10.1128/MCB.21.11.3671-3683.2001
M3 - Article
C2 - 11340161
AN - SCOPUS:0034996666
SN - 0270-7306
VL - 21
SP - 3671
EP - 3683
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 11
ER -