Abstract：
:Proliferation of endothelial cells is regulated by angiogenic and antiangiogenic factors whose actions are mediated by complex interactions of multiple signaling pathways. Both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) stimulate cell proliferation and activate the mitogen-activated protein kinase (MAPK) cascade in bovine brain capillary endothelial (BBE) cells. We have extended these findings to show that both mitogens activate MAPK via stimulation of Raf-3. Activation of Raf/MAPK is inhibited by increasing intracellular cAMP levels pharmacologically or via stimulation of endogenously expressed beta-adrenergic receptors. Both VEGF- and bFGF-induced Raf-1 activity are blocked in the presence of forskolin or 8-bromo-cAMP by 80%. The actions of increased cAMP appear to be mediated by cAMP-dependent protein kinase (PKA), since treatment with H-89, a the specific inhibitor of PKA, reversed the inhibitory effect of elevated cAMP levels on mitogen-induced cell proliferation and Raf/MAPK activation. Moreover, elevations in cAMP/PKA activity inhibit mitogen-induced cell proliferation. These findings demonstrate, in cultured endothelial cells, that the cAMP/PKA signaling pathway is potentially an important physiological inhibitor of mitogen activation of the MAPK cascade and cell proliferation.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
D'Angelo G,Lee H,Weiner RIsubject
Has Abstractpub_date
1997-12-01 00:00:00pages
353-66issue
3eissn
0730-2312issn
1097-4644pii
10.1002/(SICI)1097-4644(19971201)67:3<353::AID-JCBjournal_volume
67pub_type
杂志文章abstract：:The lining of the trachea consists of a pseudostratified, mucociliary epithelium that under a variety of conditions, such as vitamin A deficiency, toxic and mechanical injury, becomes a stratified squamous epithelium. Several in vitro cell culture models have been established to study the process of differentiation of...
journal_title：Journal of cellular biochemistry
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journal_title：Journal of cellular biochemistry
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journal_title：Journal of cellular biochemistry
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更新日期：2011-01-01 00:00:00
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journal_title：Journal of cellular biochemistry
pub_type： 杂志文章
doi：10.1002/jcb.20992
更新日期：2006-10-01 00:00:00
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journal_title：Journal of cellular biochemistry
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journal_title：Journal of cellular biochemistry
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journal_title：Journal of cellular biochemistry
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更新日期：2017-12-01 00:00:00
